cancer topics for research papers

Cancer Biology

Focus areas.

The mission of the Department of Cancer Biology is to identify and understand the causes of cancer, to develop innovative approaches to reduce cancer incidence, to create and test novel and more effective therapies, and to translate these findings into clinical care for the benefit of patients.

Research in our department is highly collaborative and is potentiated through close interactions with other basic science departments and translated through clinical collaborations.

Our faculty members are aligned into eight research focus areas that address cancer development, progression and treatment.

Cancer disparities

While cancer affects everyone, certain groups have higher rates of cancer cases, deaths and health complications. These differences can be associated with genetics, sex, racial and ethnic populations, socioeconomic status, or specific geographic areas. Studying the factors that lead to cancer disparities leads to more-effective prevention and treatment approaches for the affected populations.

• Read more about the cancer disparities focus area .

Cancer stem cells

The stem cell theory of cancer proposes that among the many different types of cells within a cancer, there exists a subpopulation of cells called cancer stem cells that multiply indefinitely, are resistant to chemotherapy, and are thought to be responsible for relapse after therapy. Cancer stem cells also give rise to highly metastatic cells that spread to other organs and tissues within the body. A deeper understanding of cancer stem cells is leading to better implementation of existing anti-cancer therapies and identification of new approaches that target the cancer stem cells specifically.

• Read more about the cancer stem cells focus area .

Cancer systems biology

Cancer is a complex disease with many molecular, genetic and cellular causes. Considering these causes as a system of interactions can lead to a better understanding of the processes involved in the development of cancer and response to therapies. Cancer systems biology integrates advanced experimental models, insights from genome sequencing and other large-scale data projects, and computational models to create unified models of cancer behavior.

• Read more about the cancer systems biology focus area .

Oncogenic gene dysregulation and carcinogenesis

Cancer initiates from genetic alterations, including mutations, deletions and copy number gains, that function to activate cancer-promoting pathways or to block processes that normally inhibit cancer development. Through better understanding of pro- and anti-cancer signaling processes and how they become dysregulated in carcinogenesis and tumor progression, our team can improve biological tools for clinicians and devise molecularly targeted therapies to intervene.

• Read more about the oncogenic gene dysregulation and carcinogenesis focus area .

Precision cancer medicine and translational therapeutics

Cancers develop and respond to therapies differently from one patient to the next. A better understanding of the specific processes driving cancer growth and spread in an individual patient allows for tailored therapeutic strategies that are more effective with minimal side effects. Profiling the mutations and abnormalities that drive a tumor, in combination with development of experimental models that assess the specific responses of cancer cells to therapeutics that target those abnormalities, has dramatically improved outcomes in many cancer types.

• Read more about the precision cancer medicine and translational therapeutics focus area .

Tumor immunology and immunotherapy

Therapeutic strategies that stimulate the immune system to target cancer cells can lead to long-lasting tumor regression and minimize relapse. Integrated efforts of laboratory researchers and clinicians are leading to improved knowledge of how the immune system interacts with cancer cells and how immune processes can be intentionally manipulated for therapeutic effect.

• Read more about the tumor immunology and immunotherapy focus area .

Tumor invasion and metastasis

A fundamental property of malignant tumor cells is the ability to invade surrounding tissues and to metastasize to other organs. These abilities underlie the majority of cancer-associated deaths. While invasion and metastasis are often thought of as the final stages of tumor development, recent studies have shown that tumor spread can occur even at early stages of tumor development, sometimes even before the primary tumor has been identified. Development of therapies targeting invasion and metastasis has the promise to significantly reduce cancer mortality.

• Read more about the tumor invasion and metastasis focus area .

Tumor microenvironment

Tumors require complex interactions with surrounding blood vessels, immune cells, supportive tissue structures and cell types that are distinct to the tumor site in order to grow, become invasive and metastasize. Tumors influence their microenvironment by releasing soluble signals that lead to degradation and remodeling of the tissue structures that constrain their growth. Targeting the interactions of tumors with the microenvironment is an important and developing area of study.

• Read more about the tumor microenvironment focus area .

More about research at Mayo Clinic

• Research Faculty
• Laboratories
• Core Facilities
• Centers & Programs
• Departments & Divisions
• Clinical Trials
• Institutional Review Board
• Postdoctoral Fellowships
• Training Grant Programs
• Publications

Mayo Clinic Footer

• Request Appointment
• About Mayo Clinic
• About This Site

Legal Conditions and Terms

• Terms and Conditions
• Privacy Policy
• Notice of Privacy Practices
• Notice of Nondiscrimination
• Manage Cookies

Advertising

Mayo Clinic is a nonprofit organization and proceeds from Web advertising help support our mission. Mayo Clinic does not endorse any of the third party products and services advertised.

• Advertising and sponsorship policy
• Advertising and sponsorship opportunities

Reprint Permissions

A single copy of these materials may be reprinted for noncommercial personal use only. "Mayo," "Mayo Clinic," "MayoClinic.org," "Mayo Clinic Healthy Living," and the triple-shield Mayo Clinic logo are trademarks of Mayo Foundation for Medical Education and Research.

353 Cancer Essay Topic Ideas & Examples

🏆 best cancer topic ideas & essay examples, 👍 good essay topics on cancer, 📌 most interesting cancer topics to write about, 💡 good research topics about cancer, ⭐ simple & easy cancer essay titles, 🔎 interesting topics to write about cancer.

• Different Applications of Calculus in Cancer Treatment and Monitoring The type of treatments applied is pre-determined by the location, the type, and the severity of the tumors. The mathematical concept of calculus is applied when doctors consider the diffusion of different drugs into the […]
• Best Practices in Breast Cancer Care Based on this, the final stage of therapy should include comprehensive support for patients with breast cancer as one of the main health care practices within the framework of current treatment guidelines.
• Breast Cancer Symptoms and Causes The mammogram is the first indication of breast cancer, even though other indications such as the presence of the lymph nodes in the armpits are also the early indications of breast cancer.
• Descriptive Data Statistics: National Cancer Institute The definitions for the measures presented are as follows: Mean = sum of all data points / number of data points; Median = the value that’s exactly in the middle when it is ordered from […]
• Breast Cancer: Concept Map and Case Study Each member of the interdisciplinary team involved in treating patients with cancer and heart disease should focus on educational priorities such as:
• Esophageal Cancer Overview and Analysis Esophageal Cancer mainly refers to the growths that forms within the tissues that line the walls of the esophagus; the tube composed of muscles that aid the passage of the food from the exterior opening […]
• Health Psychology: Going Through a Breast Cancer Diagnosis He is unaware that she has been diagnosed with depression and that she is going for breast screening Stress from work is also a contributing factor to her condition.
• American Cancer Society History Its main duty is to ensure there is a reduction of the number of patients suffering from cancer and eradication of the disease as one of the major health problem faced by many Americans today.
• Genes Cause Breast Cancer Evidence suggests the role of BRCA1 in DNA repair is more expansive than that of BRCA2 and involves many pathways. Therefore, it is suggested that BRCT ambit containing proteins are involved in DNA repair and […]
• Decision-Making in Cancer MDT The healthcare industry in the UK has integrated the concept of MDT in an effort to lower the rate of mortality as a result of cancer. The decision to incorporate the concept of MDT in […]
• Enhancing Cancer Screening Access and Treatment Equity Increasing the accessibility and equity in cancer screening solutions is extremely important. The existing screening criteria should be expanded through changes in guidelines, and increased funding.
• Progress in Cancer Control: Rhetorical Analysis According to their study, these behaviors are more likely to lead to cancer, and the authors’ goal is to convince the audience that they should take responsibility for their health and strive to minimize the […]
• Breast Cancer and Its Population Burden The other objectives that are central to this paper are highlighted below: To determine which group is at a high risk of breast cancer To elucidate the impact of breast cancer on elderly women and […]
• Pap Smear and Cervical Cancer: Oncology Nursing The piece of legislation I believe has most significantly affected women’s healthcare in the past century is the regulation for women to take Pap smear regularly to prevent cervical cancer development.
• Colorectal Cancer Screening Methodology CRC affects the colon, the large intestine, and the rectum a passageway between the colon and the anus. In 2019, the average incidence rate for CRC in the United States was 41.
• Screening Colonoscopy for Colorectal Cancer Prevention Colonoscopy allows visualization of the entire mucosa of the distal terminal ileum and the large intestine. Before the screening, the natural history of the disease is essential for the practitioner to identify the prevention levels.
• Prostate Cancer: Urinary Frequency and Incontinence In terms of the back and spine pain that the patient reported, it is notable that the x-ray revealed some mild degenerative changes in the form of a cystic mass near the spine.
• Discussion: Understanding of Cancer Annually, the IARC estimates the number of new cancer cases and fatalities worldwide and in the United States and gathers the most up-to-date data on the prevalence of cancer in populations.
• Ovarian Cancer: Risk Factors, Health Disparities, and Preventive Measures The most common signs and symptoms of ovarian cancer include weight loss, pain in the pelvic region, swelling and bloating in the abdomen, low appetite, and increased urination.
• Mindfulness Practice During Adjuvant Chemotherapy for Breast Cancer She discusses the significance of the study to the nursing field and how nurses can use the findings to help their patients cope with stress.
• The Role of hnRNPs in Acute Myeloid Leukemia Blood and lymph are tissues of mesenchymal origin, which consist of plasma and corpuscles suspended in it and form the internal environment of the body.
• Benefits of Good Nutrition During Cancer Treatment Eating various foods is an important part of a healthy diet to get the nutrients the patient needs to fight cancer.
• Community-Based Health Education on Cervical Cancer Through awareness, women will be able to understand the life of the diseases and the control measures that should be put in place to eradicate the infection.
• Antioxidants: The Role in Preventing Cancer and Heart Disease Some of antioxidants are more widely known as vitamins E, C, and carotenoids, and have a reputation of preventing cardiovascular diseases and cancer.
• The Lung Cancer Incidence Research The attributed risk is calculated by dividing the newly diagnosed incidence of cancer attributed to smoking by the total number of newly diagnosed cases of lung cancer.
• Breast Cancer: The Effective Care Domain Information about how the patient is seen, how often the patient is seen, and whether she will return for mammograms can be collected and analyzed to verify the successful intervention to extend consistency with mammograms.
• Colorectal Cancer Screening and Its Effect on Disease Incidence The purpose of this quantitative quasi-experimental quality improvement project was to determine if or to what degree the implementation of the Agency for Healthcare Research and Quality’s System Approach to Tracking and Increasing Screening for […]
• The Burden of Cancer in the United States Both Hispanic men and women are the least affected by lung cancer in terms of incidence and mortality. Therefore, considering the DALYs measure and smoking rates in the Hispanic group, it can be concluded that […]
• Statistical Analysis of Lung and Bronchus Cancer Data Using the mean obtained, the Black community has recorded the highest cases of lung and bronchus cancer, with the lowest ethnic group recording, such being the Hispanic race.
• Garden Pesticide and Breast Cancer Therefore, taking into account the basic formula, the 1000 person-years case, the number of culture-positive cases of 500, and culture-negative of 10000, the incidence rate will be 20 new cases.
• Breast Cancer as a Genetic Red Flag It is important to note that the genetic red flags in Figure 1 depicted above include heart disease, hypertension, and breast cancer.
• Breast Cancer Surveillance Consortium Analysis Simultaneously, the resource is beneficial because it aims to “improve the delivery and quality of breast cancer screening and related outcomes in the United States”.
• Drinking Green Tea: Breast Cancer Patients Therefore, drinking green tea regularly is just a necessity- it will contribute to good health and physical vigor throughout the day and prevent severe diseases.
• Pathophysiology of Chronic Obstructive Pulmonary Disease and Lung Cancer It is also evident that the illness acts fast due to the continuous multiplication of the cancer cells leading to breathing disruptions and eventual death. This sustained weight loss is primarily essential to the advancement […]
• Breast Cancer Prevention: Ethical and Scientific Issues Such information can potentially impact the patient and decide in favor of sharing the information about the current condition and risks correlating with the family history.
• Prostate Cancer Statistics for a Term Paper Prostate cancer is also known as ‘Carcinoma of the Prostate’ and it starts when cells in the prostate glands develop an abnormality that allows them to grow out of control.
• Colorectal Cancer: Promoting a Healthy Diet The aims and goals were to analyze the goals, techniques of solution, and outcomes of particular research and enhance knowledge about the topic area based on a review of freshly released data. I would also […]
• Colorectal Cancer Development Due to Dietary Habits A fundamental research interest of the present dissertation was to run a pilot test on a small sample to assess the possibility of using questionnaires as a tool to assess Saudis’ perception of dietary habits […]
• Cancer Patients’ Late Admission to a Hospice Mulville et al.set out to evaluate and identify the reasons that prevent timely admission to the hospice of cancer patients at the end of life.
• Breast Cancer: Epidemiology, Risks, and Prevention In that way, the authors discuss the topics of breast cancer and obesity and the existing methods of prevention while addressing the ethnic disparities persistent in the issue.
• Breast Cancer Development in Black Women With consideration of the mentioned variables and target population, the research question can be formulated: what is the effect of nutrition and lifestyle maintained on breast cancer development in black women?
• Dietary Habits as a Risk Factor of Colorectal Cancer The risks, however, reduce with the adoption of healthy dietary habits, such as the intake of fresh fruits and vegetables. The author advised conducting more qualitative studies on factors affecting the Saudis population to adhere […]
• Traditional and Complementary Medicine Among Indigenous Cancer Patients Therefore, it is necessary to increase the overall understanding of the role of CAM among breast cancer patients alongside identifying the key motivating factors, where the prime manifestations of the phenomenon are faith and prayer.
• Mechanisms Behind Cancer Development This shows that epigenetics can be employed to determine the type of cancer an individual is expected to develop and make it easier to detect the disease at its early stages. Thus, the combination of […]
• Education for Parents of Children With Cancer The hospital was selected because I am have been working there for a long time, and the personnel is willing to help me with the implementation of the process.
• Health Inequities in Cancer Patients Despite a recent slowdown in overall spending, the United States spends more on health care than other high-income nations and still has some of the worst health results.
• 177Lu-PSMA Radioligand Therapy for Prostate Cancer The therapy is proved to be safer and more effective than its alternatives, with a great deal of success in reducing PSMA.
• Lung Cancer: Diagnostics and Treatment Thus, it is essential to invest in research about lung cancer and be aware of the factors that contribute to its emergence to protect themselves.
• Khalaf’s Burden of Pancreatic Cancer Study Analysis The outcome factors in this study are that regular-dose and low-dose Aspirin were observed to decrease the risk of pancreatic cancer.
• Cancer Blood Tests Saving Lives It is important to note that the article explores novel ways of cancer diagnostics and screening methods using blood tests for various signs of the condition.
• Breast Cancer in Miami Florida The situation with the diagnosis of breast cancer is directly related to the availability of medicine in the state and the general awareness of the non-population.
• 177LU-PSMA Radiological Therapy of Prostate Cancer More clinical trials are necessary to define the efficacy of PSMA treatment and develop more concomitant medication. Also, Gafia et al.found that PSMA is a long-term clinical condition whose changes in management are observed after […]
• Cancer Among Aboriginal and Torres Strait Islander People When compared to non-Indigenous Australians, Aboriginal and Torres Strait Islander people, also known as Indigenous Australians, are disadvantaged across a number of health and socioeconomic indices.
• The Ethical Problem in the Case of the Cancer Patient On the other hand, urgently inducing the patient’s death may have been an administrative problem for the patient, and it is not sure that it was caused by the wife’s deliberate decision.
• Cancer Treatment Strategies and Challenges Inspired by the merits of the natural nanovesicles and the state of the art of the advanced engineering versatility of synthetic nanomaterials, we previously presented the synthetic and biological hybrid exosomes for targeted synergistic chemo […]
• Urinary Tract Infections and Pancreatic Cancer The laboratory technician is supposed to culture the urine and use Gram’s staining method to detect the microbes in the sample. The practitioners used a combination of mecillinam and cefotaxime to manage the condition.
• Patient HealthCare: Early Diagnosis of Cancer The NCQA describes the three patients’ interventions and explains how the Nurse Practitioner explicitly measures the listed interventions’ effects. While the patient is in the clinic for routine care, problems with preventive tests and their […]
• Machine Learning Algorithms in Cancer Detection One of the most fundamental tools for machine learning in cancer detection is the use of imaging, with the premise that prognostic data is embedded in pathology images and digital pathology can provide big data […]
• Acute Lymphoblastic Leukemia and Nutritional Influences A complete blood count is used to determine the precise number of each blood cell type in an individual, whereas a peripheral blood smear is used to determine alteration in the appearance and mobility of […]
• Breast Cancer: Genetics and Malignancy In the presence of such conditions, the formation of atypical cells is possible in the mammary gland. In the described case, this aspect is the most significant since it includes various details of the patient’s […]
• Video Consultations Between Patients and Clinicians in Diabetes, Cancer, and Heart Failure Services For example, during one of my interactions with the patient, I was asked whether the hospital had the policy to avoid face-to-face interaction during the pandemic with the help of video examinations.
• Diets to Prevent Heart Disease, Cancer, and Diabetes In order to prevent heart disease, cancer, and diabetes, people are required to adhere to strict routines, including in terms of diet. Additionally, people wanting to prevent heart disease, cancer, and diabetes also need to […]
• Skin Cancer: Description, Causes, and Treatment Skin cancer is one of the most common types of cancer; the three most common types of skin cancer are basal cell carcinoma, squamous cell carcinoma, and melanoma.
• Acute Lymphoblastic Leukemia, Its Prevalence and Incidence The purpose of this paper is to present the first part of the case study by describing the disease’s pathophysiology, treatment options, prevalence, and incidence.
• Colon Cancer: Symptoms, Genes, and Immunosuppression Colon cancer is the type of cancer that starts in the large intestine, which is the last section of the digestive tract.
• Acute Lymphoblastic Leukemia: Causes, Origin, and Gene Mutation Apart from analyzing chromosome abnormalities present in patients with ALL, the purpose of this paper is to investigate the disorder’s origin, including primary causes and the process of gene mutations.
• Researching the Colon Cancer and Nursing It is critical for the nurse to have trusted information about cancer tumors because many studies have indicated that patients appreciate and rely on the competence of nurses.
• Nebraska State Department of Health Registries for Cancer and Immunization There is a need to report the progress of breast cancer in Nebraska to help do more research on preventing and introducing improved chemotherapy plans. Nebraska state has immunization and cancer registries which are helpful […]
• Cancer Terminology and Characteristics Carcinomas arise from epithelial tissue, lymphomas are cancers of lymphatic tissue, leukemias are cancers of blood-forming cells, and sarcomas come from connective tissue.
• The Cancer Cell Development: Causes and Sources Loss of function of suppressor genes resulting from mutations becomes the cause of cancer development: the cell divides abnormally, increasing the cell mass of the tissue.
• Chronic Myelogenous Leukemia and Granulocytosis: Causes and Treatment The accumulation of the underdeveloped stem cells impairs the functioning of the blood cells resulting in such diseases as cancer. This is because white blood cells are part of the immune system and help fight […]
• Epidemiology: Lung Cancer Risk The continued exploration of the factors, as well as agents, leading to the spread of pandemics led to a quantitative and qualitative examination and the development of immunization to reduce infections.
• Case Study for a Patient With Cancer Because Julia refused to continue chemotherapy and radiation treatment, her adenocarcinoma should be expected to get worse, which means she may need further services of a nurse, who would create plans for supportive care; as […]
• Financing of Public Health Initiative on Prostate Cancer Additionally, they need to demonstrate to the public that the resources bestowed on them are adding value to the facilities they are in charge of.
• Genetic Testing: Screening for Colon Cancer This disorder is characterized by the development of hundreds of thousands of adenomatous polyps in the colon and rectum early in life.
• Cancer: Causes, Diagnostic and Treatment This article recommends that the new dietary patterns can be used to reduce the risk of cancer and other diseases. Vegetables can be used to reduce the occurrence of stomach cancer and colorectal cancer.
• Prostate Cancer Among Blacks in Maryland: Public Health Initiative This paper evaluates the economic principles underlying community health needs assessment of the initiative and the health economics relevant to the utilization of the service.
• New Gene Discovered That Stops Spread of Cancer At this point, it is crucial to mention that the discovery by the Salk institute is just a beginning of a long scientific journey that is anticipated to culminate in a comprehensive and conclusive study […]
• Do Cellphones Cause Brain Cancer? The reason for the worries is that cellphones emit RF energy that contains both electric and magnetic energy, and exposure to it may be unhealthy for a human being.
• Cancer Survivorship and Reproductive Health Outcomes This life includes the social, emotional, psychological, and financial effects that start at the beginning of diagnosis and commences up to the final stage of the disease.
• Patients With Cancer: The Importance of Early Referrals to Hospitals The purpose of this study was to prove the connection between early referrals to hospitals for patients with cancer and the possibility of a positive outcome of treatment for them.
• Aspects of Testicular Cancer The cancer is narrowed to the testicles and the epididymis as the tumor markers level reads normal at the first stage and has not grown into the blood.
• New Venture: Cancer Risks of Firefighters In my opinion, being a firefighter is not just a profession, it is the ability to come to the rescue, to have compassion, to feel pain, and to empathize with people who are in a […]
• Acute Myeloid Leukemia: Genetic Features of Black Patients According to the researcher, the differences in the biological impact of disease and the socioeconomic factors play a crucial role in the disparity between the Blacks and the Whites in the recovery process.
• Cancer Alley and Environmental Racism One of the sources under study is valuable, as it examines the current situation of the coronavirus and the impact of pollution on human health.
• Cancer: Risk, Treatment and Prevention Cancer is a condition characterized by abnormal cells that do not function usefully in the body, thereby destroying normal body tissues.
• Colon Cancer: Treatment Options, Medication Research Colon cancer typically begins in the large intestine, which is at the end of the digestive tract and is called a colon.
• Managing Patient With Pancreatic Cancer Overall, pancreatic cancer affects the cellular functioning of the pancreas and disrupts the operation of the digestive system. PanIN is the most common antecedent of pancreatic cancer and occurs in the small pancreatic ducts.
• Cancer Medication and Treatment Alternatives: Project Proposal Indeed, despite the advances made in the management of cancer, particularly, the surgical removal of the tumor and the following therapy allowing to reduce health risks, cancer remains one of the major causes of death […]
• Asbestos, Carcinogens, and Occupational Cancers: Insights from Dr. Demers With the cases of asbestos-related cancer rising and the vast amounts of asbestos existing in buildings, water pipes, and workplaces, there is a dire need for stringent policies to remove all asbestos from the environment.Dr.
• Does the Sun Radiation Cause Skin Cancer? Moreover, from the article written by American Cancer Society, it is evident that Ultraviolet A and Ultraviolet B from the sun lead to skin cancer.
• Light Use in Cancer Treatment The notable strength of this article is that it goes further to identify ZnPc-Q1 as a possible candidate for using light therapy in the treatment of cancer. In this work, the authors examine and describe […]
• The Virus That Causes Throat Cancers The research article used after the insight of the summary in the New York Times was from the journal of American medical association.
• Esophageal Cancer: Credible Internet Information Esophageal cancer has become one of the main forms of cancers which usually causes a lot of suffering to patients due to immense pain, difficulty in swallowing or dysphagia.
• Breast Cancer. Service Management The trial specifically looks at the effect on breast-cancer mortality of inviting women to screening from age 40 years compared with invitation from age 50 years as in the current NHS breast-screening programme.
• Fibrocystic Breast Condition or Breast Cancer? The presence of the fibrocystic breast condition means that the tissue of the breast is fibrous, and cysts are filled with the liquid or fluid. The main characteristic feature of this cancer is that it […]
• Cervical Cancer: Causes and Treatment Cervical cancer develops in the cervix – the lower part of the uterus. It starts in a particular part of the cervix, where its squamous and glandular cells connect.
• Analysis in Epidemiology: “Epithelial Ovarian Cancer and Oral Contraceptives” Therefore, in the current case, since the use of combination oral contraceptives reduces the occurrence of epithelial ovarian cancer, then the factors that affect the OCs MUST ALWAYS precede the factors affecting the occurrence of […]
• Coping With Stress in Breast Cancer Patients Therefore, it is important for research experts to ensure and guarantee adherence to methodologies and guidelines that define scientific inquiry. However, various discrepancies manifest with regard to the initiation and propagation of research studies.
• Breast Self-Examination and Breast Cancer Mortality Though it is harsh to dismiss self-exams entirely due to studies that indicate little in deaths of women who performed self-exams and those who did not, the self-exams should not be relied on exclusively as […]
• Breast Self-Exams Curbing Breast Cancer Mortality The results of the study were consistent with the findings of other studies of the same nature on the effectiveness of breast self-examination in detecting and curbing breast cancer.
• Prostate Cancer: Pathophysiology and Diagnostics The disease is normally multimodal in the prostate gland and just about 70% of the illness exists in the or the Peripheral zone.
• Cancer: Factors of Prevention and Treatment The paper focuses on studying polyploidy/multinucleated giant cancer cells, calcium, BXL Protein, Acetylsalicylic Acid, and their specific roles in the prevention and treatment of cancer.
• Herbal Therapy for Cancer Herbal therapy is a theoretical and practical medicine based on the scientific study and use of medicinal plants or drugs obtained from them for therapeutic or prophylactic purposes.
• An Approach to Care of Cancer Overview Suspecting the presence of ovarian cancer is primarily based on a number of symptoms, especially abnormal physical examination, CT and NRI scans of the abdomen as well as the pelvis region.
• Taxol Effectiveness in Inhibiting Breast Cancer Cells The following were the objectives of this experiment: To determine the effectiveness of Taxol in inhibiting breast cancer cells and ovarian cancer cells using culture method.
• Control Breast Cancer: Nursing Phenomenon, Ontology and Epistemology of Health Management Then, the evidence received is presented in an expert way leading to implementation of the decision on the management of the disease.
• Leukemia: Causes, Pathogenesis, Morphological Changes, Basic Management Studies are ongoing to establish the exact cause of the disease, which is still unknown according to the Leukemia and Lymphoma Society.
• MD Anderson Cancer Center: Community Health Assessment The focus of the assessment is the city of Houston, Texas, and the MD Anderson Cancer Center. Most health issues are related to income disparities, immigration status, and the insurance status of Houston residents.
• Researching the Ovarian Cancer In the European continent, for every 100,000 females, 12 to 17 will have ovarian cancer, depending on the nation of origin; this is the age-standardized rate. BRCA1 and BRCA2 profoundly account for the prevalence of […]
• Local Inflammation and Human Papillomavirus Status of Head and Neck Cancers The objective of the study was to assess whether periodontitis is related to the human papillomavirus status of the head and neck squamous cell carcinoma.
• Throat Cancer With Diagnosis of Human Papillomavirus The infection by the HPVs often appears in the epithelium, particularly in the areas with tissue lesions. In this respect, by means of the RNA scope, it is possible to transcribe the HPV genome and […]
• Breast Cancer: Effects of Breast Health Education The design of the research focused on research variables like skills, performance, self-efficacy, and knowledge as the researchers aimed at examining the effectiveness of these variables among young women who underwent training in breast cancer […]
• Community Nursing Role in Breast Cancer Prevention However, early detection still remains important in the prevention and treatment of breast cancer. The community has thus undertaken activities aimed at funding the awareness, treatment and research in order to reduce the number of […]
• Radiotherapy: The Efficient Cancer Treatment Method The main purpose for the proposal of this policy is to increase the safety levels and promote efficiency in the delivery of radiotherapy services to patients.
• Measuring the Uncertainty in Children With Cancer The Limitations of using Mishel Uncertainty Illness Scale and Children Uncertainty Illness Scale led to the development of Uncertainty scale for kids.
• Self-Examination and Knowledge of Breast Cancer Among Female Students Shin, Park & Mijung found that a quarter of the participants practiced breast self-examination and a half had knowledge regarding breast cancer.
• Prognosis in Ulcerative Colitis for Risk of Cancer After that the attempt was to extract the information about incidence of colon cancer in populations previously diagnosed with ulcerative colitis, to check whether the cancer risk increased with the duration of disease and finally […]
• “Tracking Breast Cancer Cells on the Move” by Gomis The article serves the purpose of examining the role of NOG, a gene that is essential in bone development and its role in breast cancer.
• Nutritional Assessment for Cancer Patients The consumption of fatty fish and a reduction in the consumption of unhealthy fats can reduce the risk of colon cancer that is brought about by the consumption of animal fat.
• Cancer Treatment Measures in the Sydney Cancer Center Overall, the study enhanced the proper understanding of the effectiveness through the analysis of the number of health specialists working in the Sydney Cancer Centre and the number of cancer patients attended per day.
• Association Between Pre-Diagnostic Circulating 25-(OH) D and Cancer This was what made the authors to undertake an investigation on correlation between pre-diagnostic of circulating 25- D concentration in the body and dietary intakes of vitamin D and calcium with colon and rectum cancer […]
• Sonodynamic Therapy for Cancer Treatment Sonodynamic therapy also known as ultrasound therapy is a hopeful innovative cancer treatment method that focuses on synergistic effect on tumor cell killing of a photosensitizer and ultrasound. Cavitation refers to the growth, oscillation and […]
• The Relationship Between Cancer and Lifestyle In addition, other lifestyle aspects, such as cigarette smoking, sun exposure and stress need to be addressed to reduce the risks of cancer.
• Cancer: Angiogenesis, Recent Research, Ethical Concerns Zayed et al.’s research reveals that the CIB1 protein controlling the endothelial cell functions is the same as the one causing red blood cell formation in cancer tumors.
• Breast Cancer Survivorship: Are African American Women Considered? The finding of the analysis is that the issue of cancer survivorship is exclusive, developing, and at the same time it depends on what individuals perceive to be cancer diagnosis as well as personal experiences […]
• Gaining Ground on Breast Cancer: Advances in Treatment The article by Esteva and Hortobagyi discusses breast cancer from the aspect of increased survival rates, the novel treatments that have necessitated this and the promise in even more enhanced management of breast cancer.
• Pain Management in Hillman Cancer Center’s Patients Medical and surgical approaches are considered to be the main ways for pain treatment in cancer patients. Advanced stages of cancer result into a multidimensional pain and are where the clinical psychologists step in.
• Ovarian Cancer: Description and Treatment In applying various treatment options, it is important for doctors to ensure that they understand all options, means of navigating through the process, as well as the development stage of the cancer.
• Effects of Hypoxia, Surrounding Fibroblasts, and p16 Expression on Breast Cancer The study was conducted to determine whether migration and invasion of breast cancer cells were stimulated by hypoxia, as well as determining whether the expression of p16 ectopically had the potential to modulate the cell […]
• Breast Cancer: Preventing, Diagnosing, Addressing the Issue In contrast to the MRI, which presupposes that the image of the tissue should be retrieved with the help of magnetic fields, the mammography tool involves the use of x-rays.
• Smoking and Lung Cancer Among African Americans Primarily, the research paper provides insight on the significance of the issue to the African Americans and the community health nurses.
• Acute Lymphocytic Leukemia in Adult Patients Acute lymphocytic leukemia is the cancer of the blood and the bone marrow. The final type of lymph cells is natural killer cells whose role in the body is to nullify the effect of cancerous […]
• Dietary Fat Intake and Development of Breast Cancer This study aimed to determine the relationship between dietary fat intake and the development of breast cancer in women. The outcome of the study strongly suggests that there is a close relationship between a high […]
• The Detection and Diagnosis of Breast Cancer The severity of cancer depends on the movement of the cancerous cells in the body and the division and growth or cancerous cells.
• Smoking and Cancer in the United States In this research study, data on tobacco smoking and cancer prevalence in the United States was used to determine whether cancer in the United States is related to tobacco smoking tobacco.
• Prostate Cancer: Preventive Approaches and Treatment However, the case of prostate cancer seems to oppose this ideology; hence, the purpose of this paper is to understand preventive approaches and therapies used to manage prostate cancer.
• Skin Cancer: Comparison of Samples The aim of this experiment is to examine and thereafter represent low and high power illustrations of a normal skin specimen and of skin specimens that have been affected by various forms types of skin […]
• The Female Reproductive System and Ovarian Cancer The ovary is the one of the central organs of the female reproductive system. The zona granulosa is the exterior layer of cells enclosing the follicles.
• Property Rights to the Cancer Genes The easiest way to understand the protection of patents and the rationale behind them is by appreciating the fact that patents are part of human rights.
• Dietary Approach to Colon Cancer Prevention These research findings appear to support the hypothesis that the presence of folate in the diet is linked to the risk factor for colon cancer.
• Treatment of Ovarian Cancer Factors that predispose women to ovarian cancer include infertility, use of certain medication, hormone replacement therapy, use of oral contraceptives, and party.
• The Pennsylvania Cancer Registry (PCR) This data is essential in that, doctors or clinical experts are able to identify the form of treatment to be provided to each cancer patient, to follow up on the patients’ progress, give any necessary […]
• Breast Cancer: WMI Research and the Current Approaches Although the conclusions provided by the WHI in the study conducted to research the effects of estrogen and progesterone cessation on the chance of developing a breast cancer do not comply with the results of […]
• Oesophageal Cancer as a Global Health Concern The incidence of oesophageal cancer is high in various parts of the world, but for the purposes of this paper, China will be the region of focus.
• Using Genetically-Modified Bacteria to Fight Cancer at Johns Hopkins To do so, a concise summary of the article will be provided, followed by a review of its relevance to the course.
• Skin Cancer and Sunlight: Case Control, Cohort, and Clinical Trial Design The main component in sunlight that is said to be responsible for the development of skin cancer is the Ultraviolet emission.
• Battle Against Cancer in New York State On the other hand, the cancer goals for New York target to reduce the new forms of the disease as well as the various disabilities and body deformations resulting from cancer.
• Various Proteins Targets for Lung, Breast and Colorectal Cancers This protein has been identified in recent research as the one playing the biggest role in causing the growth and the spread of cancer in the lungs.
• Global Health Organization – World-Cancer Campaign The organization can collaborate with other organizations such as the World Economic Forum and the International Council of Nurses to tackle the cancer crisis.
• Healthcare: Colon Cancer The colon refers to the longest section of the large gut and the most low-down section of the digestive arrangement in the human body.
• Dosage & Regimen for MEK Inhibitor: Cancer Clinical Trial The study is a treatment trial aimed at designing the correct dose of GSK1120212. The trial is aimed at determining the dosage and regimen for MEK inhibitor that should be mixed with everolimus in order […]
• Breast Cancer Susceptibility Gene (BRCA2) The mechanisms underlying the genetic predisposition to a particular disease are manifold and this concept is the challenging one to the investigators since the advent of Molecular Biology and database resources.
• Prostate Cancer Pathophysiology and Management At the moment, the use of tumour markers such as kallikrein is the most widespread method of differentiating these two disorders.
• Terminal Cancer Patients: Community Nursing The sole purpose of any nursing activity during any given kind of illness and end-of-life stage is to maximize the quality of life and functioning for individuals, families, and the community at large.
• Ovarian Cancer Overview and Analysis However, several factors have been deemed to contribute to the risk of developing ovarian cancer, for instance, the lesser children a woman has and the later in life she bears children, the higher the chances […]
• Prediction of Breast Cancer Prognosis It has been proposed that the fundamental pathways are alike and that the expression of gene sets, instead of that of individual genes, may give more information in predicting and understanding the basic biological processes.
• The Genetic Basis of Human Cancer This is one of the most difficult in curing, as it may affect any part of the body, and seriously damage the body tissues.
• Breast Cancer Survivors: Effects of a Psychoeducational Intervention While the conceptual framework is justified in analysis of the quality of life, there is the likelihood of influence of the context with quality of life adopting different meanings to patients in different areas and […]
• Cancer and Oxygenation: Oxygen as a Remedy for Cancer
• Cancer: Gene Mutation’s Influence, Treatments
• The Effective Pain Assessment in Patients With Lung Cancer
• Providers’ Role in Quality Assurance in Breast Cancer Screening
• Framing Qualitative Research on Lung Cancer
• Oncology: Colorectal Cancer
• Prostate Cancer: Symptoms and Treatment
• Clinical Laboratory Science of Breast Cancer
• Induced and Spontaneous Abortion and Breast Cancer Incidence Among Young Women
• Quality of Life in Chronic Leukemia Patients
• Dyspnea in Cancer Patients
• Ovarian Cancer: Medical Review
• Lung Cancer Cells Migrating to Other Parts of the Body
• Prostate Cancer: The Ion Channels
• To Live Until You Die: Palliative Care in Cancer Experience
• Care Needs of Children Whose Parents Have Incurable Cancer
• New Screening Guidelines for Breast Cancer
• Breast Cancer in Afro- and Euro-Americans
• Cancer Treatment and Life Quality in Adult Patients
• Breast Cancer Assessment in London
• Oral Cancer Reconstruction
• Skin Cancer Awareness Overview
• Angiostatic Approaches to Cancer Therapy
• Genetics of Prostate Cancer and Physical Features
• Epithelial Ovarian Cancer Investigation
• Creativity in People With Cancer
• Cancer: Alternative and Complementary Therapies
• Promotion of Cardiovascular Health and Cancer Prevention
• Cancer Longitudinal Exploration
• Breast Cancer: At-Risk Population, Barriers, and Improvement
• Effective Solutions to the Prevention of Cervical Cancer
• Breast Cancer: Moral and Medical Aspects
• Breast Cancer and AIDS: Significant Issues in the United States in the Late 20th Century
• Breast Cancer Risk Factors: Genetic and Nutritional Influences
• Breast Cancer Genetics & Chromosomal Analysis
• The Role Genetics Information Plays in Treating Cancer
• Breast Cancer: The Case of Anne H.
• Leukemia Types: Characteristics, Genetics, and Symptoms
• CRISPR and Cas-9 Technology as the Solution to Cancer
• Colon Cancer: Risk Factors
• World Health Organization Cancer Website Tool
• Long Distance Cancer Treatment Ethics
• A Community Capacity-Enhancement Approach to Breast and Cervical Cancer Screening
• The Role of Inflammation in Cancer
• Cognitive Behavioral Therapy: Plan for Cancer Pain
• Psychosocial Factors & Immune Mechanisms in Cancer Regulation
• Fundraising Methods for the Canadian Cancer Society
• Nutrition and Cancer Rates
• Breast Cancer Diagnosis Procedure in Saudi Arabia
• Language and Stigmatization: Cancer, HIV, and AIDS
• The Three Most Common Types of Cancer in America
• Breast Cancer and the Effects of Diet
• J. Overcash on Older Adults With Cancer
• Postmenopause Hormone Therapy and Endometrial Cancer
• Risk Factors for Cervical Cancer
• When the Smoke Clears: The Story About the Lung Cancer
• Motivational Interviewing as a Smoking Cessation Intervention for Patients With Cancer
• Genetic Predisposition to Breast Cancer: Genetic Testing
• Cancer Pathophysiology and Nursing Management
• Breast Cancer: Causes and Treatment
• Integumentary System Diseases. Skin Cancer and Eczema
• Digestive Cancer. Complementary & Alternative Treatment
• The History of Cervical Cancer: Treatment and Care
• Ethics of Leukemia Treatment With Disabled HIV Cells
• Human Papillomavirus Infection and Cervical Cancer
• Colorectal Cancer Care Coordination
• Penectomy Challenges in Cancer Patients
• Monoclonal Antibodies in Treating Breast Cancer
• The American Cancer Society’s Website Evaluation
• Acute Lymphocytic and Myelogenous Leukemia in Children
• Viruses as a Cause of Cancer
• Cancer and Chemotherapy Effects on Patients
• Chronic Diseases: Heart Failure and Cancer
• Pain Reduction Metods for Cancer Patients
• Lung Cancer Stages, Complications, and Support
• Breast Cancer: Women’s Health Initiative & Practices
• Hormone Receptor-Positive Breast Cancer Pathophysiology
• Cervical Cancer and Women’s Health
• Complex Fibroadenoma and Breast Cancer Risk
• Cannabis and Cancer Pain Management
• Breast Cancer: Health Psychology Plan
• Colorectal Cancer Patient’s Discharge Planning
• Cancer Epidemic Research and Expectations
• Carcinoma in Situ Management Options
• Cancer Epidemiology in the United States
• Understanding Pathophysiology of Cancers
• Registered Nurses and Cancer Patients
• ”Preferences for Photographic Art Among Hospitalized Patients With Cancer” by Hanson ET Al.
• Pain Assessment for Cancer Patients: Literature Search
• Keytruda as an Innovative Cancer Control Tool
• Oncology: Innovative Solutions to Fight Cancer
• Cancer, Its Nature and Gene Therapy
• Body pH and Cancer Occurrence Correlation
• Cancer: Psychological Effects and Coping Strategies
• Complementary and Alternative Medicine for Women With Breast Cancer
• Alcohol and Smoking Impact on Cancer Risk
• Ovarian Cancer: Causes, Symptoms, and Treatment
• Establishing a Cancer Treatment Unit in a Hospital
• Cancer Behavior in the Elderly: Cognitive-Affective Analysis
• Cancer Alley: Environmental Justice Analysis
• Lung Cancer and Cystic Fibrosis: Diagnosis and Care
• Trinity Community Hospital’s Cancer Service Line
• Blood Test and Cancer Spread in Children
• Reverse Mutation Concept in Cancer Biology
• Cancer and Tumor Suppressor Genes
• Skin Cancer: Diagnosis and Treatment
• Benign Prostatic Hyperplasia and Prostate Cancer
• Thyroid Cancer Chemotherapy
• Chronic Lymphocytic Leukemia and Immunoglobulin M
• Colorectal Cancer Screening in the USA
• Breast Cancer Screening in Young American Women
• Hyperbaric Oxygen Therapy for Cancer Patients
• Prostate Cancer Among African Americans in NYC
• Prostate Cancer Among African American Men in New York
• Hexokinase 2 Enzyme in Cancer Treatment
• Depression and Cancer in Caucasian Female Patient
• Cancer Screening in Lesbians, Gays, Transgenders
• Cancer Epidemiology for American Population
• Air Pollution as a Factor for Renal Cancer
• Children With Cancer and Their Social Activities
• Cancer Treatment Effects on Sexual Function
• Protein Diet, Telomere Length, and Cancer
• Community-Based Participatory Research on Cancer
• Nursing for Metastatic Pancreatic Cancer Patient
• Children With Cancer and Schooling Challenges
• Epigenetics and Its Role in Cancer Detection and Prevention
• Screening for Breast Cancer
• The Role of Epigenetics in Cancer: Contributors to the Formation of Cancer Tumors
• Cancer and Women’s and Men’s Health
• Prostate Cancer: Causes, Symptoms, Treatment
• Prostate Cancer and Age-Related Risk Factors
• Gua Sha in Cancer Therapy Against Myalgia
• Gastric Cancer Diagnosis and Treatment
• Cervical Cancer and Risk Factors
• Annual Breast Cancer Awareness Campaign
• Cervical Cancer: Medical Imaging and Radiotherapy
• Testicular Cancer: Diagnosis and Treatment
• Organic Foods Consumption and Cancer Prevention
• Prostate Cancer, Its Genetics and Prevention Methods
• Cancer Epidemiology Among Chinese Americans
• Colorectal Cancer, Diagnosis and Treatment Plan
• Cervical Cancer, Its Nature and Symptoms
• Prostate Cancer Symptoms and Laboratory Tests
• Skin Cancer in Australia and Health Campaign
• Breast Cancer Patients’ Life Quality and Wellbeing
• Obesity as a Risk Factor for Uterine Cancer
• Palliative Care for Cancer Patients: Search Strategies
• Palliative Care for Adult Cancer Patients
• Palliative Care for Adult Patients With Cancer
• Breast Cancer Patients’ Functions and Suitable Jobs
• Peptic Ulcer Disease and Stomach Cancer Diagnostics
• Jordanian Breast Cancer Survival Rates in 1997-2002
• Cancer Patients’ Financial Status and Life Quality
• Breast Cancer Awareness Among African Americans
• Cancer Disease and Its Impact
• Breast Cancer Screening Among Non-Adherent Women
• Healthcare Research: Bladder Cancer Independent Variables
• Cancer Patient’s Autonomy and Medical Ethics
• The Internet Use at MD Anderson Cancer Hospital
• American Cancer Society’ Social Media Networks Usage
• Breast Cancer: Treatment and Rehabilitation Options
• The Effectiveness of Music for Cancer Patients
• Women Healthcare: Breast Cancer
• Skin Cancer: Types and Cells of Origin
• Prevention of Cancer: Good Nutrition and Positive Behavior
• Lung Cancer Disease and Prevention Methods
• Breast Cancer Public Relations Campaign
• Technologies: Improving the MD Anderson Cancer Center Website
• Explanation of Cancer Disease
• Gallbladder Cancer, Its Causes and Rates
• Health Information Seeking and Breast Cancer Diagnosis
• Stem Cell Therapy in Colorectal Cancer
• Employing Cancer Vulnerability Reduction in Ukraine
• Current Standing of Breast Cancer and Its Effects on the Society
• Descriptive Epidemiology of Cancer in the UK
• International Expansion Strategy of Australia Cancer Care Hospital.
• Medical Marijuana use for Terminal Colon Cancer
• Asbestos and Rising of Cancer
• The Problem of Skin Cancer in Australia
• Health Outcome of Tobacco Use: Lung Cancer
• Prostate Cancer Treatment
• Breast Cancer: Disease Prevention
• Breast Cancer Definition and Treatment
• Radiation Therapy for Testicular Cancer
• Breast Cancer Incidence and Ethnicity
• Treatment Options for Breast Cancer
• Cancer Treatment by Nanotechnology
• Health Risks and Prevention: Cardiovascular Disease and Cancers
• Healthcare Demographics of Prostate Cancer in the US
• Malevolence of Cancer: Pathogenesis and Treatment Options
• Risk Factors, Staging, and Treatment of Breast Cancer
• Case Management for Breast Cancer Patients
• DNA Essay Ideas
• Biochemistry Research Topics
• Genetics Research Ideas
• Human Papillomavirus Paper Topics
• Stem Cell Essay Titles
• Nursing Care Plan Paper Topics
• Health Promotion Research Topics
• Diabetes Questions
• Chicago (A-D)
• Chicago (N-B)

IvyPanda. (2024, March 2). 353 Cancer Essay Topic Ideas & Examples. https://ivypanda.com/essays/topic/cancer-essay-topics/

"353 Cancer Essay Topic Ideas & Examples." IvyPanda , 2 Mar. 2024, ivypanda.com/essays/topic/cancer-essay-topics/.

IvyPanda . (2024) '353 Cancer Essay Topic Ideas & Examples'. 2 March.

IvyPanda . 2024. "353 Cancer Essay Topic Ideas & Examples." March 2, 2024. https://ivypanda.com/essays/topic/cancer-essay-topics/.

1. IvyPanda . "353 Cancer Essay Topic Ideas & Examples." March 2, 2024. https://ivypanda.com/essays/topic/cancer-essay-topics/.

Bibliography

IvyPanda . "353 Cancer Essay Topic Ideas & Examples." March 2, 2024. https://ivypanda.com/essays/topic/cancer-essay-topics/.

Skip to Content

• Conquer Cancer
• ASCO Journals
• f Cancer.net on Facebook
• t Cancer.net on Twitter
• q Cancer.net on YouTube
• g Cancer.net on Google
• Types of Cancer
• Navigating Cancer Care
• Coping With Cancer
• Understanding the Publication and Format of Cancer Research Studies
• Understanding Cancer Research Study Design and How to Evaluate Results
• How Are Cancer Drugs Discovered and Developed?
• Drug Approval and Labeling in the United States
• Evaluating Cancer Information on the Internet
• How Patient Advocates Help Cancer Research: An Expert Q&A
• Journals and Magazines
• Clinical Trials
• ASCO Annual Meetings
• Health Disparities and Cancer
• For Patient Advocates
• Public Policy Advocacy
• Cancer Awareness Dates
• Survivorship

Introduction to Cancer Research

This section provides information on the following topics:

How studies get published and how to search for ones relevant to you

Types of research studies and how to know if the results apply to you

How new cancer drugs are found and tested

How FDA programs help new drugs reach people sooner

How to find reliable health and medical information online

How doctors and patient advocates work together to advance research

Links to leading journals and magazines about oncology and general medicine

Research and Advocacy

More in this section.

Timely. Trusted. Compassionate.

Comprehensive information for people with cancer, families, and caregivers, from the American Society of Clinical Oncology (ASCO), the voice of the world's oncology professionals.

Find a Cancer Doctor

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Chin J Cancer

The 150 most important questions in cancer research and clinical oncology series: questions 86–93

Chinese journal of cancer.

Sun Yat-sen University Cancer Center, Guangzhou, 510060 Guangdong P. R. China

Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which spark diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 8 more questions are presented as follows. Question 86. In which circumstances is good supportive care associated with a survival advantage in patients with cancer? Question 87. Can we develop animal models to mimic immunotherapy response of cancer patients? Question 88. What are the mechanisms underlying hepatitis B virus-associated non-hepatocellular cancers? Question 89. Can we more precisely target tumor metabolism by identifying individual patients who would benefit from the treatment? Question 90. What type of cranial irradiation-based prophylactic therapy combination can dramatically improve the survival of patients with extensive small-cell lung cancer? Question 91. How can postoperative radiotherapy prolong overall survival of the patients with resected pIIIA-N2 non-small cell lung cancer? Question 92. What are the key molecular events that drive oral leukoplakia or erythroplakia into oral cancer? Question 93. How could we track the chemotherapeutics-driven evolution of tumor genome in non-small cell lung cancer for more effective treatment?

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology [ 1 ]. Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology [ 2 – 12 ], which spark diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, Questions 86–93 are selected and presented. This program of collecting and publishing the key questions is still ongoing. Please send your thoughtful questions to Ms. Ji Ruan via email: [email protected].

Question 86: In which circumstances is good supportive care associated with a survival advantage in patients with cancer?

Background and implications.

It is well documented that good supportive care throughout the treatment and survival phases of cancer as well as palliative care towards the end of life improve the quality of life of the patients [ 13 ]. In some circumstances, good supportive care may also prolong survival. Quintin et al. [ 14 ] performed a global analysis of data from multiple trials and showed that quality of life and presenting symptoms were prognostic factors for survival of patients with cancer in addition to other clinical characteristics. For example, febrile neutropenia following chemotherapy is a life-threatening adverse effect and can be mitigated by giving the chemotherapy with granulocyte colony stimulating factor (G-CSF). It is well documented that mortality from infection is reduced by G-CSF [ 15 ]; however, it is not clear that this may be translated into an overall survival advantage. Prophylactic use of antiemetics increases the tolerance of chemotherapy, allowing full dose to be given and courses of chemotherapy to be completed, which has been shown to prolong survival [ 16 ]. Good symptom control with chemotherapy may also prolong survival. In a randomized study, second-line chemotherapy was given with or without early palliative care to patients with non-small cell lung cancer, and the results showed that those receiving the palliative care in addition to their chemotherapy had significantly longer survival than those receiving chemotherapy only (11.6 vs. 8.9 months, P  = 0.02) [ 17 ]. Further, it is intriguing that psychosocial support may prolong survival. A weekly psychosocial support group and self-hypnosis for pain was added to anticancer therapy for breast cancer patients in a randomized trial and resulted in prolonged survival as compared with those who only received anticancer therapy [ 18 ]. The relationship between social networks and social support has been equivocal although a large breast cancer study showed an increase in both all-cause mortality and breast cancer mortality in women who are socially isolated [ 19 , 20 ]. Certainly, the narratives of exceptional survivors of incurable cancer ascribed some of their outcomes to family support [ 21 ].

Clearly, in some circumstances, the addition of good supportive care which addresses cancer-associated symptoms and adverse effects of treatment can be added to anticancer treatment to prolong survival. More researches are needed to better define when this occurs.

Affiliation and email

Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia 5001, Australia.

[email protected].

Question 87: Can we develop animal models to mimic immunotherapy response of cancer patients?

Efforts on immuno-oncology (I/O) research to fight cancer are in exponential phase of growth due to recent breakthrough in the development of immune checkpoint inhibitors and unprecedented rate of regulatory approval to shorten the otherwise lengthy bench to bedside process. The prevalent models include syngeneic, genetically engineered, and partially humanized mouse models each with its advantages and limitations. The lack of precise animal models that would be capable of mimicking human immune microenvironment is one of the major challenges for proper preclinical evaluation of I/O therapies and identifying patients most likely to be benefited from specific I/O strategies.

The ideal animal models should also possess effective biomarkers for monitoring the immune functions of the host as well as therapeutic effects of I/O. In current clinical practice, the remarkable progress in the development of immune checkpoint inhibitors went solo without parallel advancement of definitive patient selection tool. The cost, toxicities, and the time delay for the 40%–60% of patients not benefiting from immunotherapy makes it imperative to identify valid prognostic biomarkers [e.g., programmed death-ligand 1 (PD-L1) expression, mismatch repair (MMR) deficiency, cluster of differentiation 8 (CD8) T cell infiltrates, tumor mutation burden] that could predict patient response and facilitate differentiation of durable response versus transient response. Given the dynamic nature of the immune response and the complexity of immune/tumor interaction, development of biomarkers for immunotherapies is highly challenging. Presence of tumor-specific antigens, expression of immunosuppressive molecules [PD-L1, indoleamine 2,3-dioxygenase (IDO), and so on] by tumor cells, and mutation load and landscape all contribute to the response of tumor cells to I/O therapies. While most of the biomarker-searching efforts had focused on tumor characteristics, the role of host immune system is equally important. The effectiveness of a given immunotherapeutic approach depends on a pre-existing immune state of a patient.

In summary, development of clinically relevant animal models possessing discerning prognostic markers is critical to fulfill the promise of immunotherapy as a paradigm-shifting strategy to fight the most aggressive and intractable cancers.

Qian Shi and Meng Qiao.

Affiliation and emails

Crown Biosciences Inc., Taicang, Jiangsu Province, 215400, P. R. China.

[email protected]; [email protected].

Question 88: What are the mechanisms underlying hepatitis B virus-associated non-hepatocellular cancers?

Hepatitis B virus (HBV) infection is a strong risk factor for the development of hepatocellular carcinoma. Epidemiological studies have also shown that HBV infection may increase the incidence of several types of non-hepatocellular cancers, including gastric adenocarcinoma, pancreatic ductal carcinoma, and non-Hodgkin lymphoma (NHL). Clinical studies further suggested that some of these HBV-associated non-hepatocellular cancers, for instance a subtype of NHL, diffuse large B cell lymphoma, exhibit a more aggressive disease course with poor prognosis, independent of its pathological subtype. However, what are the mechanisms underlying these associations and whether the viral infection is indeed disease-causing or rather a contributing co-factor remain unclear. Two major hypotheses, direct viral infection of the corresponding cell types and chronic viral antigen stimulations, have been proposed. In both scenarios, infection may result in dysregulation of host cellular processes and increased genome instability, and in the case of direct infection, like in hepatocellular carcinoma, integration of viral DNA into the host genome may lead to activation of selective oncogenes. More detailed morphological and molecular studies, including characterization of the genome of these HBV-associated non-hepatocellular cancers and the repertories of infiltrating immune cells, may provide further clues to this question. It will also be of interest to determine if there is an association between genotype (strain of HBV) and phenotype (type of cancer). Finally, in areas/countries with a high prevalence of infection and initiated the mandatory HBV vaccine program decades ago, theoretically, the incidence of these non-hepatocellular cancers should decrease with time. Of note, this may be complicated by the increased contribution of other risk factors, especially life style-related factors. Chronic HBV infection is endemic in some parts of Asia, Africa, and South America and remains to be a public health burden in these areas. Further understanding the molecular mechanisms underlying the HBV-associated cancers will help us to develop novel or more precise therapies for the affected patients.

Yao Liu and Qiang Pan-Hammarström.

Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska University Hospital, Huddinge, Stockholm SE 141 86, Sweden.

[email protected]; [email protected].

Question 89: Can we more precisely target tumor metabolism by identifying individual patients who would benefit from the treatment?

Background and implication.

During the process of tumorigenesis, tumor cells must face two challenges: first, obtaining the nutrients needed for the rapid growth; and second, evading the surveillance and attack from the host immune system. Tumor cell’s unique metabolic program can be used to meet these challenges. Glycolysis is the major metabolic process used by malignant tumors, even when oxygen supply is adequate, which is termed as “the Warburg effect”. Glycolysis decreases the pH value of the tumor microenvironment (TME); therefore, tumor cells can inhibit the activities of antigen-presenting cells (APCs) and cytotoxic T lymphocytes (CTLs) by controlling the acidity of TME, eventually leading to tumor cell immune escape. A second group of metabolism-related modification directly targets the major histocompatibility complex-I (MHC-I) and related molecules and hence sensitizes cancer cells to the cytolytic actions of the anti-tumor adaptive immune response.

Recent findings from in vitro and in vivo studies have shown that targeting tumor and immune cell metabolism hold the promising possibilities toward clinical therapeutics for treating cancer [ 22 , 23 ]. However, clinical benefit has only been observed in a small number of patients [ 24 – 28 ]. Most patients still do not respond to these new therapies, and nearly all patients with certain types of cancer (i.e., pancreatic and colorectal cancers) do not respond. The reason is probably because tumor metabolism may vary over the course of tumor development, or some hidden tumor metabolic products modulate signaling pathways important for immune cell activation. A new hypothesis has been proposed that tumor cells can change their metabolism by waves of gene regulation to adjust to their different needs [ 29 ]. Some of these waves are originated by deregulated expression of oncogenes, which have already been linked to metabolic remodeling. On the other hand, different parts of solid tumor sometimes possess different epigenetic characteristics and may be derived from distinct cancer stem cell populations. Therefore, the most serious challenge in reshaping the tumor-specific metabolism and immune profiles in TME is to understand the metabolic heterogeneity which is extremely complicated depending not only on tumor and immune cell types but also on tumor stages and subset of patient population.

Nevertheless, the success associated with these new approaches has opened new investigations addressing several questions: How much metabolism pathways represent true vulnerabilities for tumor development and immunosuppression in different types and stages of cancer? Are there other factors that may be blocking, even temporarily, which is critical for tumor control? How different subsets of tumor cell populations respond to metabolic intervention? Can we identify ahead of time the patients who would benefit from metabolic targeted therapy?

Notably, tumor and immune cells share similar metabolic needs and reprogramming during proliferation to support their increased biosynthetic and energy demands [ 30 , 31 ] and often compete for the same nutrients. Therefore, deprivation of nutrients in TME must be cautiously explored to eliminate potential negative impacts on the anti-tumor immunity. Understanding the underlying mechanisms of metabolic interplay between tumor and immune cells will provide new precise directions to manipulate the tumor metabolism for better treatment outcome.

Jianyang Wang and Zhouguang Hui.

Department of Radiation Oncology (JW and ZH), Department of VIP Medical Services (ZH), National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.

[email protected]; [email protected].

Question 90: What type of cranial irradiation-based prophylactic therapy combination can dramatically improve the survival of patients with extensive small-cell lung cancer?

Brain metastasis is a common reason of treatment failure in small-cell lung cancer (SCLC), particularly in extensive disease which represents approximately two-thirds of newly diagnosed SCLCs. Recent studies have found that thoracic radiotherapy (TRT) can increase the 2-year overall survival (OS) rate of patients with extensive SCLC after chemotherapy [ 32 – 34 ]. However, it remains controversial that whether prophylactic cranial irradiation (PCI) can prolong OS [ 35 – 38 ]. The combination of TRT and PCI may boost the chances of survival, but there will be not much predictable OS benefit even if more prospective studies with large sample sizes are conducted. After first-line chemotherapy, the comprehensive treatment based on TRT and PCI, such as combining with new anti-metastatic drugs, will make great strides toward OS improvement. The application of more accurately targeted therapy is now available and promising. Maintenance treatment with sunitinib can prolong progression-free survival (PFS) in extensive SCLC [ 39 ]. Recent studies on new drugs targeting the signaling pathways (e.g., Notch signaling) related to neuroendocrine differentiation, DNA reparation, and immune checkpoint are ongoing. The Notch signaling pathway influences multiple processes in normal cell morphogenesis, including the differentiation of multipotent progenitor cells (neuron differentiation), cell apoptosis, and cell proliferation. Rovalpituzumab tesirine (Rova-T) targeting the Notch signaling pathway showed promising results in a phase I trial [ 40 ]. Poly ADP-ribose polymerase (PARP) is DNA repairase and is critical in DNA damage repair. By inhibiting PARP, proliferation of malignant cells can be suppressed. Veliparib, a PARP inhibitor, has yielded antitumor activity in SCLC [ 41 ]. Researches on immunotherapy primarily focus on cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors. Nivolumab alone and in combination with ipilimumab resulted in encouraging response rates (RR) in a phase I/II trial in the relapsed tumor setting [ 42 ]. The development of anti-metastasis agents is clearly critical for further improving the survival benefits of the patients with extensive SCLC. In addition, advanced irradiation technique is expected to be adopted in future clinical trails to decrease irradiation-induced injury in hippocampus for protecting cognitive function [ 43 ].

Lei Deng and Zhouguang Hui.

Department of Radiation Oncology (LD and ZH), Department of VIP Medical Services (ZH), National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.

[email protected]; [email protected].

Question 91: How can postoperative radiotherapy prolong overall survival of the patients with resected pIIIA-N2 non-small cell lung cancer?

For patients with resected pIIIA-N2 non-small cell lung cancer (NSCLC), the main reason of treatment failure is locoregional and/or distant relapse. Adjuvant chemotherapy can prolong overall survival to some extent. However, the role of postoperative radiotherapy is not well defined.

A meta-analysis study on postoperative radiotherapy published in 1998 concluded that postoperative radiotherapy did not prolong the survival, even in patients with stage III and pN2 NSCLC, which may due to the toxicities with suboptimal, outdated irradiation equipment and techniques [ 44 ]. Improvements in conformal radiotherapy techniques have led to a resurgence of interest in studying the effect of postoperative radiotherapy on pIIIA-N2 NSCLC. Several retrospective, large-size, case–control studies have shown that postoperative radiotherapy using three dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiation therapy (IMRT) techniques can prolong overall survival [ 45 ]. However, the benefit still needs to be confirmed by randomized clinical trials (RCTs). Up to now, there are three such phase III RCTs. CALGB 9734, the earliest one, failed because of slow accrual [ 46 ]. LUNGART, the ongoing one, began in 2007 and aims to enroll 700 patients by its conclusion in 2022. The other ongoing phase III multi-center RCT ( {"type":"clinical-trial","attrs":{"text":"NCT00880971","term_id":"NCT00880971"}} NCT00880971 ), conducted by our institute, has accrued 400 patients over planned 500 patients. However, due to the heterogeneity of pIIIA-N2 NSCLC, only certain subgroups of patients may benefit from postoperative radiotherapy. Selecting suitable candidates or the populations at high risk who may benefit from postoperative radiotherapy is the next and profound task.

It is expected that by combining with targeted therapy and/or immunotherapy, the therapeutic effects of postoperative radiotherapy can be enhanced. For patients with completely resected NSCLC with epidermal growth factor receptor (EGFR) activating mutation, two recently reported RCTs have showed that adjuvant EGFR tyrosine kinase inhibitors (TKIs) significantly prolonged disease-free survival as compared with adjuvant chemotherapy [ 47 , 48 ]. Therefore, for pIIIA-N2 NSCLC patients with EGFR-activating mutation receiving EGFR TKIs, the value of postoperative radiotherapy should be further evaluated. Theoretically, any new agent that can inhibit metastasis could enhance the efficacy of postoperative radiotherapy, and more efforts are warranted in this direction.

Yu Men and Zhouguang Hui.

Department of VIP Medical Services, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.

[email protected]; [email protected].

Question 92: What are the key molecular events that drive oral leukoplakia or erythroplakia into oral cancer?

The natural history of cancer is poorly understood. The main reason is that in the vast majority of the cases, malignant tumors are diagnosed after becoming clinically perceptible. The paradox is that, for patients dying from cancer, the time from diagnosis to death is often much shorter than the long period preceding diagnosis. Most of our knowledge is based on the analysis of established malignant tumors in comparison with histologically normal tissue, and the use of naturally occurring or genetically engineered animal models that may not recapitulate the natural history of human cancer. Initiation is thought to be the first step of the multistep model of cancer development, followed by promotion and progression. However, the stepwise and sequential progression model is being challenged by some clinical observations. One of the best examples is the natural history of oral leukoplakia or erythroplakia, the most frequent, potentially malignant lesions of the oral cavity. They can remain for many years without changing, can regress spontaneously or after cessation of tobacco smoking, alcohol drinking, or smokeless tobacco, and can transform to invasive squamous cell carcinoma (SCC) at the same site or at distance from the potentially malignant lesion. The reported rate of malignant transformation has been low in community-based studies in developing countries (0.06% per year) and higher in observational studies in western countries involving patients followed in hospital-based academic centers (1%–5% per year) [ 49 ].

We believe that the longitudinal and spatial dynamics of early-stage tumorigenesis in the oral cavity through comprehensive evaluation of cellular and molecular changes in the epithelial and stromal cells represent a unique setting to get more insight into the natural history of carcinomas. The disease is prevalent in different parts of the world and associated with various environmental agents: in western countries, it frequently affects patients with smoking and alcohol drinking history in the form of oral leukoplakia, whereas in Southeast Asia it frequently affects patients consuming areca nut, betel leaf, and quid who preferentially develop erythroplakia. Of note, oral potentially malignant lesions and SCC negative for human papillomavirus affecting patients with no smoking or alcohol drinking history, although representing a minority of all patients, have an increasing incidence over the past decades for unknown reasons. The oral cavity is easily accessible, and it is considered to be a molecular mirror of molecular alterations induced by smoking in the upper and lower aerodigestive tract. Prospectively validated in situ biomarkers of risk (e.g., loss of heterozygocity at prespecified chromosomal sites) can be used to define cohorts of patients with potentially malignant lesions at high risk of developing oral cancer. These elements represent a strong rationale for intensive exploration in this unique setting. It has the potential to foster international collaborations toward the better understanding of the biology of early-stage tumorigenesis, and provide an opportunity to develop personalized prevention strategies that will benefit patients far beyond the decreased incidence of oral cancer.

Pierre Saintigny.

Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon; Department of Translational Research and Innovation, and Department of Medical Oncology, Centre Léon Bérard, Lyon, 69008, France.

[email protected].

Question 93: How could we track the chemotherapeutics-driven evolution of tumor genome in non-small cell lung cancer for more effective treatment?

Currently, effective drug treatments for the patients with non-small cell lung cancer (NSCLC) comprise mainly of standard platinum-based cytotoxic treatment, targeted therapies including inhibitors for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and immunotherapy. However, treatment resistance will inevitably occur in most patients after a certain period of time. This is believed to be partially caused by the heterogeneity in tumor genome. Cancer is a genomic disease, and cancer genome constantly undergoes changes under selective pressure from anticancer drug treatment. This alteration is also named tumor evolution, which partially explains acquired drug resistance. For example, some acquired secondary mutations, e.g., EGFR C797S, have been detected in the patient who initially harbors EGFR T790M mutation when resistance against first-line EGFR inhibitor occurs. Therefore, there is a need to dynamically monitor tumor clonal evolution in NSCLC patients. Methods for monitoring tumor evolution include multiregional sequencing and liquid biopsies. In multiregional sequencing, tumor masses from several regions are sequenced in parallel through next-generation sequencing. In liquid biopsies, a serial of circulating molecules or cells in the blood including circulating tumor DNAs (ctDNAs) and circulating tumor cells (CTCs) could reflect the information of tumor genome. These methods could represent the whole tumor genomic landscape and reflect tumor heterogeneity. In addition to this, longitudinal or serial monitoring tumor genome through liquid biopsies or multiregional sequencing could keep track of the tumor genome in both time and space. Of course, it remains a technical challenge in collecting biopsy samples from multiple time points in the same patient. Advances in imaging-guided transthoracic biopsy of lung lesions are the hope for delivering personalized treatments in response to the evolving tumor genome for dramatically improving treatment outcomes in NSCLC patients.

Yi Xiong and Zhi-Xing Lu.

Xiangya school of medicine, Central South University, Changsha, Hunan 410008, P. R. China.

[email protected]; [email protected].

• Alzheimer's disease & dementia
• Arthritis & Rheumatism
• Attention deficit disorders
• Autism spectrum disorders
• Biomedical technology
• Diseases, Conditions, Syndromes
• Endocrinology & Metabolism
• Gastroenterology
• Gerontology & Geriatrics
• Health informatics
• Inflammatory disorders
• Medical economics
• Medical research
• Medications
• Neuroscience
• Obstetrics & gynaecology
• Oncology & Cancer
• Ophthalmology
• Overweight & Obesity
• Parkinson's & Movement disorders
• Psychology & Psychiatry
• Radiology & Imaging
• Sleep disorders
• Sports medicine & Kinesiology
• Vaccination
• Breast cancer
• Cardiovascular disease
• Chronic obstructive pulmonary disease
• Colon cancer
• Coronary artery disease
• Heart attack
• Heart disease
• High blood pressure
• Kidney disease
• Lung cancer
• Multiple sclerosis
• Myocardial infarction
• Ovarian cancer
• Post traumatic stress disorder
• Rheumatoid arthritis
• Schizophrenia
• Skin cancer
• Type 2 diabetes
• Full List »

share this!

May 21, 2024

This article has been reviewed according to Science X's editorial process and policies . Editors have highlighted the following attributes while ensuring the content's credibility:

fact-checked

peer-reviewed publication

trusted source

Researchers develop new tool for better classification of inherited disease-causing variants

by Children's Hospital of Philadelphia

Researchers from Children's Hospital of Philadelphia (CHOP), the Perelman School of Medicine at the University of Pennsylvania, and the National Cancer Institute (NCI) of the National Institutes of Health have developed a new tool that allows scientists to annotate variant data from large-scale studies with clinically-focused classifications for risk of childhood cancer and other diseases. This new tool brings older applications in line with current guidelines and is available for use—for free—in the research community. The tool was described in a paper recently published in the journal Bioinformatics .

Whole genome and exome sequencing have become more widely available tools for clinical research in identifying inherited (germline) genetic variants that could result in a variety of diseases. While guidelines from the American College of Medical Genetics-Association for Molecular Pathology (ACMG-AMP) are frequently updated to help clinicians determine if germline variants are likely responsible for a patient's disease, automated tools may not always keep pace with such updates.

"Our goal was to create a publicly available tool that could evolve with these guidelines while still using many of the critical databases and approaches the research community has come to know," said senior study author Sharon J. Diskin, Ph.D., a member of the faculty of the Department of Biomedical and Health Informatics at CHOP and Associate Professor of Pediatrics at Penn Medicine.

The new tool, Automated Germline Variant Pathogenicity (AutoGVP), integrates germline variant pathogenicity annotations—information about whether identified variants cause disease—from the ClinVar database and sequence variant classifications from a modified version of the tool InterVar. AutoGVP returns pathogenicity classifications based on evolving ACMG-AMP guidelines through integration of ClinVar and InterVar. It addresses the InterVar tool's potential to overinterpret pathogenicity from loss-of-function variants that reduce the activity of a particular gene.

The need for AutoGVP became clear following a study published by Diskin and colleagues last year in the Journal of the National Cancer Institute that analyzed the germline DNA sequencing of 786 neuroblastoma patients and identified 116 pathogenic or likely pathogenic variants. The authors also reported that patients carrying these germline variants had a worse survival probability and identified BARD1 as an important neuroblastoma predisposition gene with both common and rare germline pathogenic or likely pathogenic variations.

A team including authors from the JNCI paper collaborated on the development of AutoGVP, to facilitate large-scale annotation of germline variants and assign pathogenicity automatically. They are applying AutoGVP to genetic data from pediatric brain tumor patients and larger neuroblastoma cohorts.

"Many samples we use for identifying pathogenic variants in pediatric brain tumors come from the centralized resource of the Children's Brain Tumor Network (CBTN), and we would like to be able to share new findings with the CBTN sites in a more streamlined manner," said Jo Lynne Rokita, Ph.D., a Supervisory Bioinformatics Scientist at the Center for Data-Driven Discovery (D3B) at CHOP and co-senior author of the study.

"With AutoGVP, we can streamline variant classification and swiftly incorporate new information as more and more biobanks release large sequencing data," said first author Jung Kim, Ph.D., a staff scientist at Division of Cancer Epidemiology and Genetics at the NCI. "Furthermore, AutoGVP reduces hands-on curating of variants and allows for reproducibility of the variant curation."

Explore further

Feedback to editors

HPV vaccines prevent cancer in men as well as women, new research suggests

36 minutes ago

Study suggests psychedelic drug-induced hyperconnectivity in the brain helps clarify altered subjective experiences

Over 750,000 antimicrobial resistance deaths preventable yearly via vaccines, water, sanitation and infection control

10 hours ago

Poor access to essential surgery is costing lives, says study

Research reveals that more people died from hot or cold weather conditions than COVID-19 in parts of UK

12 hours ago

Upgrading brain storage: Quantifying how much information our synapses can hold

Propensity score matching offers more efficient biomarker discovery in cancer research

14 hours ago

Study uncovers cell type-specific genetic insights underlying schizophrenia

A promising approach to develop a birth control pill for men

Sequencing of the developing human brain uncovers hundreds of thousands of new gene transcripts

Related stories.

Guidance on clinical management of CHEK2 pathogenic variants and cancer risks

Jul 25, 2023

Study shows expanded cancer gene testing feasible, beneficial for patients

Feb 26, 2024

Mortality up for breast cancer diagnosed five to 10 years after childbirth

Apr 25, 2024

Cancer-predisposition variants associated with adverse outcomes in rhabdomyosarcoma

Mar 28, 2024

Early-onset colorectal cancer germline genetic differences identified by race, ethnicity

Jun 30, 2023

Germline genomic profiles of children, young adults with solid tumors to inform management and treatment

May 5, 2020

Recommended for you

Inhibiting a metabolic pathway provides new approach to Epstein-Barr virus and resulting diseases

Tracking the cellular and genetic roots of neuropsychiatric disease

Researchers develop experimental mRNA avian flu vaccine

16 hours ago

Let us know if there is a problem with our content

Use this form if you have come across a typo, inaccuracy or would like to send an edit request for the content on this page. For general inquiries, please use our contact form . For general feedback, use the public comments section below (please adhere to guidelines ).

Please select the most appropriate category to facilitate processing of your request

Thank you for taking time to provide your feedback to the editors.

Your feedback is important to us. However, we do not guarantee individual replies due to the high volume of messages.

E-mail the story

Your email address is used only to let the recipient know who sent the email. Neither your address nor the recipient's address will be used for any other purpose. The information you enter will appear in your e-mail message and is not retained by Medical Xpress in any form.

Newsletter sign up

Get weekly and/or daily updates delivered to your inbox. You can unsubscribe at any time and we'll never share your details to third parties.

More information Privacy policy

Donate and enjoy an ad-free experience

We keep our content available to everyone. Consider supporting Science X's mission by getting a premium account.

E-mail newsletter

Two decades of studies suggest health benefits associated with plant-based diets

But researchers caution against broad diet recommendations until remaining knowledge gaps are filled.

Vegetarian and vegan diets are generally associated with better status on various medical factors linked to cardiovascular health and cancer risk, as well as lower risk of cardiovascular diseases, cancer, and death, according to a new review of 49 previously published papers. Angelo Capodici and colleagues present these findings in the open-access journal PLOS ONE on May 15, 2024.

Prior studies have linked certain diets with increased risk of cardiovascular disease and cancer. A diet that is poor in plant products and rich in meat, refined grains, sugar, and salt is associated with higher risk of death. Reducing consumption of animal-based products in favor of plant-based products has been suggested to lower the risk of cardiovascular disease and cancer. However, the overall benefits of such diets remain unclear.

To deepen understanding of the potential benefits of plant-based diets, Capodici and colleagues reviewed 48 papers published between January 2000 and June 2023 that themselves compiled evidence from multiple prior studies. Following an "umbrella" review approach, they extracted and analyzed data from the 48 papers on links between plant-based diets, cardiovascular health, and cancer risk.

Their analysis showed that, overall, vegetarian and vegan diets have a robust statistical association with better health status on a number of risk factors associated with cardiometabolic diseases, cancer, and mortality, such as blood pressure, management of blood sugar, and body mass index. Such diets are associated with reduced risk of ischemic heart disease, gastrointestinal and prostate cancer, and death from cardiovascular disease.

However, among pregnant women specifically, those with vegetarian diets faced no difference in their risk of gestational diabetes and hypertension compared to those on non-plant-based diets.

Overall, these findings suggest that plant-based diets are associated with significant health benefits. However, the researchers note, the statistical strength of this association is significantly limited by the many differences between past studies in terms of the specific diet regimens followed, patient demographics, study duration, and other factors. Moreover, some plant-based diets may introduce vitamin and mineral deficiencies for some people. Thus, the researchers caution against large-scale recommendation of plant-based diets until more research is completed.

The authors add: "Our study evaluates the different impacts of animal-free diets for cardiovascular health and cancer risk showing how a vegetarian diet can be beneficial to human health and be one of the effective preventive strategies for the two most impactful chronic diseases on human health in the 21st century."

• Diet and Weight Loss
• Diseases and Conditions
• Colon Cancer
• Endangered Plants
• Veterinary Medicine
• Colorectal cancer
• Ovarian cancer
• Polyphenol antioxidant
• Stomach cancer
• Cervical cancer
• HPV vaccine
• Breast cancer

Story Source:

Materials provided by PLOS . Note: Content may be edited for style and length.

Journal Reference :

• Angelo Capodici, Gabriele Mocciaro, Davide Gori, Matthew J. Landry, Alice Masini, Francesco Sanmarchi, Matteo Fiore, Angela Andrea Coa, Gisele Castagna, Christopher D. Gardner, Federica Guaraldi. Cardiovascular health and cancer risk associated with plant based diets: An umbrella review . PLOS ONE , 2024; 19 (5): e0300711 DOI: 10.1371/journal.pone.0300711

Cite This Page :

Explore More

• Treating Cataracts and Other Eye Conditions
• Early Arrival of Palaeolithic People On Cyprus
• Networks Regulating Gene Function in Human Brain
• Birth of Universe's Earliest Galaxies
• Why the Brain Can Robustly Recognize B&W Images
• Birth Control Pill for Men?
• Intriguing World Sized Between Earth, Venus
• Billions of Orphan Stars Revealed
• Massive Catalog of Strange Worlds
• Mental Disorders May Spread Thru Social Networks

Trending Topics

Strange & offbeat.

Brain and Spinal Cord Tumor Research Results and Study Updates

See Advances in Brain and Spinal Cord Tumor Research for an overview of recent findings and progress, plus ongoing projects supported by NCI.

The activity of 34 genes can accurately predict the aggressiveness of meningiomas, a new study shows. This gene expression signature may help oncologists select the best treatments for people with this common type of brain cancer than they can with current methods.

An NCI-supported study called OPTIMUM, part of the Cancer Moonshot, was launched to improve the care of people with brain tumors called low-grade glioma in part by bringing them into glioma-related research.

Treating craniopharyngioma often requires surgery, radiation therapy, or both. But results of a study suggest that, for many, combining the targeted therapies vemurafenib (Zelboraf) and cobimetinib (Cotellic) may substantially delay, or even eliminate, the need for these treatments.

In a large clinical trial, vorasidenib slowed the growth of low-grade gliomas that had mutations in the IDH1 or IDH2 genes. Vorasidenib is the first targeted drug developed specifically to treat brain tumors.

Researchers have found that the aggressive brain cancer glioblastoma can co-opt the formation of new synapses to fuel its own growth. This neural redirection also appears to play a role in the devastating cognitive decline seen in many people with glioblastoma.

Two companion studies have found different forms of some brain tumors, diffuse midline glioma and IDH-mutant glioma, become dependent for their survival on the production of chemicals called pyrimidines. Clinical trials are planned to test a drug that blocks pyrimidine synthesis in patients with gliomas.

The combination of dabrafenib (Tafinlar) and trametinib (Mekinist) shrank more brain tumors, kept the tumors at bay for longer, and caused fewer side effects than chemotherapy, trial results showed. The children all had glioma with a BRAF V600 mutation that could not be surgically removed or came back after surgery.

Two separate but complementary studies have identified a new way to classify meningioma, the most common type of brain tumor. The grouping system may help predict whether a patient’s tumor will grow back after treatment and identify new treatments.

A nanoparticle coating may help cancer drugs reach medulloblastoma tumors in the brain and make the treatment less toxic. Mice treated with nanoparticles containing palbociclib (Ibrance) and sapanisertib lived substantially longer than those treated with either drug alone.

A new test could potentially be used to identify children treated for medulloblastoma who are at high risk of their cancer returning. The test detects evidence of remaining cancer in DNA shed from medulloblastoma tumor cells into cerebrospinal fluid.

Standard radiation for medulloblastoma can cause long-term damage to a child’s developing brain. A new clinical trial suggests that the volume and dose of radiation could be safely tailored based on genetic features in the patient’s tumor.

In people with glioblastoma and other brain cancers, steroids appear to limit the effectiveness of immunotherapy drugs, a new study shows. The findings should influence how steroids are used to manage brain tumor symptoms, researchers said.

Results from two studies show that a liquid biopsy that analyzes DNA in blood accurately detected kidney cancer at early and more advanced stages and identified and classified different types of brain tumors.

A method that combines artificial intelligence with an advanced imaging technology can accurately diagnose brain tumors in fewer than 3 minutes during surgery, a new study shows. The approach can also accurately distinguish tumor from healthy tissue.

Glioblastoma cells sneak many copies of a key oncogene into circular pieces of DNA. In a new NCI-funded study, scientists found that the cells also slip several different genetic “on switches” into these DNA circles, helping to fuel the cancer’s growth.

Men and women with glioblastoma appear to respond differently to standard treatment. A new study identifies biological factors that might contribute to this sex difference.

A liquid biopsy blood test can detect DNA from brain tumors called diffuse midline gliomas, researchers have found. This minimally invasive test could be used to identify and follow molecular changes in children with these highly lethal brain tumors.

Despite continued efforts to develop new therapies for glioblastoma, none have been able to improve how long patients live appreciably. Despite some setbacks, researchers are hopeful that immunotherapy might be able to succeed where other therapies have not.

Progress against the brain cancer glioblastoma has been slow. Drs. Mark Gilbert and Terri Armstrong of NCI’s Neuro-Oncology Branch discuss why and what’s being done to change that.

Studies presented at the 2017 AACR annual meeting suggest that therapies which take advantage of the mutations in the IDH gene may be more effective than drugs that block it.

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Review Article
• Published: 13 May 2024

Cancer therapy with antibodies

• Suman Paul   ORCID: orcid.org/0000-0001-9357-3702 1 ,
• Maximilian F. Konig   ORCID: orcid.org/0000-0001-5045-5255 2 ,
• Drew M. Pardoll 1 ,
• Chetan Bettegowda 3 ,
• Nickolas Papadopoulos 1 ,
• Katharine M. Wright 4 ,
• Sandra B. Gabelli   ORCID: orcid.org/0000-0003-1205-5204 4 ,
• Mitchell Ho   ORCID: orcid.org/0000-0002-9152-5405 5 ,
• Andrea van Elsas   ORCID: orcid.org/0009-0001-3426-2653 6 &
• Shibin Zhou   ORCID: orcid.org/0000-0003-1941-4425 1  

Nature Reviews Cancer ( 2024 ) Cite this article

3769 Accesses

96 Altmetric

Metrics details

• Antibody therapy
• Cancer immunotherapy
• Cancer therapy
• Drug development

The greatest challenge in cancer therapy is to eradicate cancer cells with minimal damage to normal cells. Targeted therapy has been developed to meet that challenge, showing a substantially increased therapeutic index compared with conventional cancer therapies. Antibodies are important members of the family of targeted therapeutic agents because of their extraordinarily high specificity to the target antigens. Therapeutic antibodies use a range of mechanisms that directly or indirectly kill the cancer cells. Early antibodies were developed to directly antagonize targets on cancer cells. This was followed by advancements in linker technologies that allowed the production of antibody–drug conjugates (ADCs) that guide cytotoxic payloads to the cancer cells. Improvement in our understanding of the biology of T cells led to the production of immune checkpoint-inhibiting antibodies that indirectly kill the cancer cells through activation of the T cells. Even more recently, bispecific antibodies were synthetically designed to redirect the T cells of a patient to kill the cancer cells. In this Review, we summarize the different approaches used by therapeutic antibodies to target cancer cells. We discuss their mechanisms of action, the structural basis for target specificity, clinical applications and the ongoing research to improve efficacy and reduce toxicity.

This is a preview of subscription content, access via your institution

Access options

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

24,99 € / 30 days

cancel any time

Subscribe to this journal

Receive 12 print issues and online access

195,33 € per year

only 16,28 € per issue

Buy this article

• Purchase on Springer Link
• Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Antibody-based cancer therapy

Emerging new therapeutic antibody derivatives for cancer treatment

The present and future of bispecific antibodies for cancer therapy

Data availability.

The data used to make Figs.  1 and  6 are available from the American Cancer Society and the Antibody Society .

Sternberger, L. A. & Sternberger, N. H. Monoclonal antibodies distinguish phosphorylated and nonphosphorylated forms of neurofilaments in situ. Proc. Natl Acad. Sci. USA 80 , 6126–6130 (1983).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Stark, S. E. & Caton, A. J. Antibodies that are specific for a single amino acid interchange in a protein epitope use structurally distinct variable regions. J. Exp. Med. 174 , 613–624 (1991).

Article   CAS   PubMed   Google Scholar  

Antibody therapeutics approved or in regulatory review in the EU or US. Antibody Society www.antibodysociety.org/resources/approved-antibodies (2023). The Antibody Society is an association that supports research and development of antibody-based drugs and maintains an updated list of antibodies approved by the FDA and EMA.

June, C. H. & Sadelain, M. Chimeric antigen receptor therapy. N. Engl. J. Med. 379 , 64–73 (2018).

Labanieh, L. & Mackall, C. L. CAR immune cells: design principles, resistance and the next generation. Nature 614 , 635–648 (2023).

Carter, P. Improving the efficacy of antibody-based cancer therapies. Nat. Rev. Cancer 1 , 118–129 (2001).

Weiner, G. J. Building better monoclonal antibody-based therapeutics. Nat. Rev. Cancer 15 , 361–370 (2015).

Ho, M. Inaugural editorial: searching for magic bullets. Antib. Ther. 1 , 1–5 (2018).

CAS   PubMed   PubMed Central   Google Scholar  

Kohler, G. & Milstein, C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256 , 495–497 (1975). This seminal paper describes the hybridoma technology that enabled the production of monoclonal antibodies. Kohler and Milstein received the Nobel Prize for this work.

Hwang, W. Y. & Foote, J. Immunogenicity of engineered antibodies. Methods 36 , 3–10 (2005).

Reff, M. E. et al. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83 , 435–445 (1994). This paper describes the generation of rituximab, the first chimeric antibody that demonstrated significant tumour reduction and later became the standard of care for the treatment of patients with B cell lymphomas.

Goldstein, N. I., Prewett, M., Zuklys, K., Rockwell, P. & Mendelsohn, J. Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. Clin. Cancer Res. 1 , 1311–1318 (1995).

CAS   PubMed   Google Scholar  

Looney, R. J. et al. B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum. 50 , 2580–2589 (2004).

Jones, P. T., Dear, P. H., Foote, J., Neuberger, M. S. & Winter, G. Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 321 , 522–525 (1986). This paper describes the process of CDR grafting that enabled the production of humanized antibodies. The majority of cancer antibodies utilize the humanized antibody format.

Carter, P. et al. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Natl Acad. Sci. USA 89 , 4285–4289 (1992).

Spieker-Polet, H., Sethupathi, P., Yam, P. C. & Knight, K. L. Rabbit monoclonal antibodies: generating a fusion partner to produce rabbit-rabbit hybridomas. Proc. Natl Acad. Sci. USA 92 , 9348–9352 (1995).

Zhang, Y. F. & Ho, M. Humanization of rabbit monoclonal antibodies via grafting combined Kabat/IMGT/Paratome complementarity-determining regions: rationale and examples. MAbs 9 , 419–429 (2017).

Parray, H. A. et al. Hybridoma technology a versatile method for isolation of monoclonal antibodies, its applicability across species, limitations, advancement and future perspectives. Int. Immunopharmacol. 85 , 106639 (2020).

McCafferty, J., Griffiths, A. D., Winter, G. & Chiswell, D. J. Phage antibodies: filamentous phage displaying antibody variable domains. Nature 348 , 552–554 (1990). This paper describes the early phage display technologies that enabled the selection of antibodies against a range of antigens including cancer antigens. G. Smith and G. Winter received the Nobel Prize for their work on phage display-based antibody production.

Lonberg, N. et al. Antigen-specific human antibodies from mice comprising four distinct genetic modifications. Nature 368 , 856–859 (1994). This paper describes the development of transgenic mouse models that led to the production of fully human antibodies.

Lu, R. M. et al. Development of therapeutic antibodies for the treatment of diseases. J. Biomed. Sci. 27 , 1 (2020).

Winter, G., Griffiths, A. D., Hawkins, R. E. & Hoogenboom, H. R. Making antibodies by phage display technology. Annu. Rev. Immunol. 12 , 433–455 (1994).

Lu, S. et al. The rapid and highly parallel identification of antibodies with defined biological activities by SLISY. Nat. Commun. 14 , 17 (2023).

Alfaleh, M. A. et al. Phage display derived monoclonal antibodies: from bench to bedside. Front. Immunol. 11 , 1986 (2020).

Almagro, J. C., Daniels-Wells, T. R., Perez-Tapia, S. M. & Penichet, M. L. Progress and challenges in the design and clinical development of antibodies for cancer therapy. Front. Immunol. 8 , 1751 (2017).

Article   PubMed   Google Scholar  

Booth, B. Human antibody discovery: of mice and phage. Forbes https://www.forbes.com/sites/brucebooth/2017/05/11/human-antibody-discovery-of-mice-and-phage/?sh=1f76520c7f26 (2017).

Jain, T. et al. Biophysical properties of the clinical-stage antibody landscape. Proc. Natl Acad. Sci. USA 114 , 944–949 (2017).

Douglass, J. et al. Bispecific antibodies targeting mutant RAS neoantigens. Sci. Immunol. 6 , eabd5515 (2021).

Hsiue, E. H. et al. Targeting a neoantigen derived from a common TP53 mutation. Science 371 , eabc8697 (2021). This paper describes the generation of bispecific antibodies targeting the most common oncogenic mutation (R175H) in the tumour suppressor protein p53.

Boder, E. T., Midelfort, K. S. & Wittrup, K. D. Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. Proc. Natl Acad. Sci. USA 97 , 10701–10705 (2000).

Georgiou, G. et al. Display of heterologous proteins on the surface of microorganisms: from the screening of combinatorial libraries to live recombinant vaccines. Nat. Biotechnol. 15 , 29–34 (1997).

Ho, M., Nagata, S. & Pastan, I. Isolation of anti-CD22 Fv with high affinity by Fv display on human cells. Proc. Natl Acad. Sci. USA 103 , 9637–9642 (2006).

Lipovsek, D. & Pluckthun, A. In-vitro protein evolution by ribosome display and mRNA display. J. Immunol. Methods 290 , 51–67 (2004).

Wang, J. et al. Durable blockade of PD-1 signaling links preclinical efficacy of sintilimab to its clinical benefit. MAbs 11 , 1443–1451 (2019).

Marcus, R. et al. Obinutuzumab for the first-line treatment of follicular lymphoma. N. Engl. J. Med. 377 , 1331–1344 (2017).

Vitolo, U. et al. Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma. J. Clin. Oncol. 35 , 3529–3537 (2017).

van Imhoff, G. W. et al. Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J. Clin. Oncol. 35 , 544–551 (2017).

Maloney, D. G. et al. A phase 3 randomized study (HOMER) of ofatumumab vs rituximab in iNHL relapsed after rituximab-containing therapy. Blood Adv. 4 , 3886–3893 (2020).

Rugo, H. S. et al. Margetuximab versus trastuzumab in patients with previously treated HER2-positive advanced breast cancer (SOPHIA): final overall survival results from a randomized phase 3 trial. J. Clin. Oncol. 41 , 198–205 (2023).

Price, T. J. et al. Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 15 , 569–579 (2014).

Furman, W. L. Monoclonal antibody therapies for high risk neuroblastoma. Biologics 15 , 205–219 (2021).

PubMed   PubMed Central   Google Scholar  

Peter, H. H. et al. Targeting FcRn for immunomodulation: benefits, risks, and practical considerations. J. Allergy Clin. Immunol. 146 , 479–491.e5 (2020).

Roopenian, D. C. & Akilesh, S. FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol. 7 , 715–725 (2007).

Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344 , 783–792 (2001). This is a groundbreaking clinical trial demonstrating the survival benefit of the HER2-targeting antibody trastuzumab in patients with breast cancer. Slamon received the Lasker–DeBakey award for his work related to HER2 targeting in breast cancer.

Bang, Y. J. et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376 , 687–697 (2010).

Cunningham, D. et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N. Engl. J. Med. 351 , 337–345 (2004).

Camidge, D. R. et al. Phase I study of 2- or 3-week dosing of telisotuzumab vedotin, an antibody-drug conjugate targeting c-Met, monotherapy in patients with advanced non-small cell lung carcinoma. Clin. Cancer Res. 27 , 5781–5792 (2021).

Redman, J. M., Hill, E. M., AlDeghaither, D. & Weiner, L. M. Mechanisms of action of therapeutic antibodies for cancer. Mol. Immunol. 67 , 28–45 (2015).

Mone, A. P. et al. Alemtuzumab induces caspase-independent cell death in human chronic lymphocytic leukemia cells through a lipid raft-dependent mechanism. Leukemia 20 , 272–279 (2006).

Meyer, S. et al. New insights in type I and II CD20 antibody mechanisms-of-action with a panel of novel CD20 antibodies. Br. J. Haematol. 180 , 808–820 (2018).

Vidarsson, G., Dekkers, G. & Rispens, T. IgG subclasses and allotypes: from structure to effector functions. Front. Immunol. 5 , 520 (2014).

Article   PubMed   PubMed Central   Google Scholar  

Salfeld, J. G. Isotype selection in antibody engineering. Nat. Biotechnol. 25 , 1369–1372 (2007).

Yu, J., Song, Y. & Tian, W. How to select IgG subclasses in developing anti-tumor therapeutic antibodies. J. Hematol. Oncol. 13 , 45 (2020).

Wang, X., Mathieu, M. & Brezski, R. J. IgG Fc engineering to modulate antibody effector functions. Protein Cell 9 , 63–73 (2018).

Weng, W. K. & Levy, R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J. Clin. Oncol. 21 , 3940–3947 (2003).

Musolino, A. et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J. Clin. Oncol. 26 , 1789–1796 (2008).

Golay, J. & Taylor, R. P. The role of complement in the mechanism of action of therapeutic anti-cancer mAbs. Antibodies 9 , 58 (2020).

Schneider-Merck, T. et al. Human IgG2 antibodies against epidermal growth factor receptor effectively trigger antibody-dependent cellular cytotoxicity but, in contrast to IgG1, only by cells of myeloid lineage. J. Immunol. 184 , 512–520 (2010).

Rosner, T. et al. Immune effector functions of human IgG2 antibodies against EGFR. Mol. Cancer Ther. 18 , 75–88 (2019).

Cho, H. S. et al. Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab. Nature 421 , 756–760 (2003). This study of early structural biology has improved our understanding of trastuzumab binding to the HER2 extracellular subdomain 4 to inhibit HER2 function.

Hao, Y., Yu, X., Bai, Y., McBride, H. J. & Huang, X. Cryo-EM structure of HER2-trastuzumab-pertuzumab complex. PLoS ONE 14 , e0216095 (2019).

Weisser, N. E. et al. An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity. Nat. Commun. 14 , 1394 (2023).

Rouge, L. et al. Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab. Science 367 , 1224–1230 (2020).

Liu, R., Oldham, R. J., Teal, E., Beers, S. A. & Cragg, M. S. Fc-engineering for modulated effector functions-improving antibodies for cancer treatment. Antibodies 9 , 64 (2020).

Nimmerjahn, F., Vidarsson, G. & Cragg, M. S. Effect of posttranslational modifications and subclass on IgG activity: from immunity to immunotherapy. Nat. Immunol. 24 , 1244–1255 (2023). This review describes the Fc domain modifications that alter IgG antibody effector functions.

Rugo, H. S. et al. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer: a phase 3 randomized clinical trial. JAMA Oncol. 7 , 573–584 (2021).

Ribas, A. & Wolchok, J. D. Cancer immunotherapy using checkpoint blockade. Science 359 , 1350–1355 (2018).

Le, D. T. et al. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med. 372 , 2509–2520 (2015).

Le, D. T. et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357 , 409–413 (2017). This paper demonstrates the utility of the PD1 antibody, pembrolizumab, in a range of cancer types with mismatch repair deficiency. This led to the FDA approval of pembrolizumab in any cancer with mismatch repair deficiency which was the first tissue agnostic drug approval in oncology.

Gandhi, L. et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N. Engl. J. Med. 378 , 2078–2092 (2018).

Marabelle, A. et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 21 , 1353–1365 (2020).

Nghiem, P. T. et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N. Engl. J. Med. 374 , 2542–2552 (2016).

Sharma, P. et al. The next decade of immune checkpoint therapy. Cancer Discov. 11 , 838–857 (2021).

Chamoto, K., Yaguchi, T., Tajima, M. & Honjo, T. Insights from a 30-year journey: function, regulation and therapeutic modulation of PD1. Nat. Rev. Immunol. 23 , 682–695 (2023). Together with Sharma et al. (2021), this review describes the mechanism of immune checkpoint-inhibiting antibodies in cancer. Allison and Honjo jointly received the Nobel Prize for their discoveries of a cancer therapy by inhibition of the immune checkpoint PD1.

Huard, B. et al. Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc. Natl Acad. Sci. USA 94 , 5744–5749 (1997).

Wang, J. et al. Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3. Cell 176 , 334–347.e12 (2019).

Blackburn, S. D., Shin, H., Freeman, G. J. & Wherry, E. J. Selective expansion of a subset of exhausted CD8 T cells by alphaPD-L1 blockade. Proc. Natl Acad. Sci. USA 105 , 15016–15021 (2008).

Im, S. J. et al. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 537 , 417–421 (2016).

Yost, K. E. et al. Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat. Med. 25 , 1251–1259 (2019).

Romano, E. et al. Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients. Proc. Natl Acad. Sci. USA 112 , 6140–6145 (2015).

Kim, M. J. et al. Deletion of PD-1 destabilizes the lineage identity and metabolic fitness of tumor-infiltrating regulatory T cells. Nat. Immunol. 24 , 148–161 (2023).

Sharma, A. et al. Anti-CTLA-4 immunotherapy does not deplete FOXP3 + regulatory T cells (Tregs) in human cancers. Clin. Cancer Res. 25 , 1233–1238 (2019).

Kamada, T. et al. PD-1 + regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc. Natl Acad. Sci. USA 116 , 9999–10008 (2019).

Kumagai, S. et al. The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies. Nat. Immunol. 21 , 1346–1358 (2020).

Scapin, G. et al. Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab. Nat. Struct. Mol. Biol. 22 , 953–958 (2015).

You, W. et al. A network meta-analysis comparing the efficacy and safety of anti-PD-1 with anti-PD-L1 in non-small cell lung cancer. J. Cancer 9 , 1200–1206 (2018).

Barlesi, F. et al. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study. Lancet Oncol. 19 , 1468–1479 (2018).

Lee, N. Y. et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 22 , 450–462 (2021).

Monk, B. J. et al. Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial. Lancet Oncol. 22 , 1275–1289 (2021).

Bang, Y. J. et al. Phase III, randomised trial of avelumab versus physician’s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann. Oncol. 29 , 2052–2060 (2018).

Lee, J. Y. et al. Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy. Nat. Commun. 7 , 13354 (2016).

Lee, H. T. et al. Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab. Sci. Rep. 7 , 5532 (2017).

Lee, H. T., Lee, S. H. & Heo, Y. S. Molecular interactions of antibody drugs targeting PD-1, PD-L1, and CTLA-4 in immuno-oncology. Molecules 24 , 1190 (2019).

Lin, D. Y. et al. The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. Proc. Natl Acad. Sci. USA 105 , 3011–3016 (2008).

Liu, K. et al. Structural basis of anti-PD-L1 monoclonal antibody avelumab for tumor therapy. Cell Res. 27 , 151–153 (2017).

Tang, S. & Kim, P. S. A high-affinity human PD-1/PD-L2 complex informs avenues for small-molecule immune checkpoint drug discovery. Proc. Natl Acad. Sci. USA 116 , 24500–24506 (2019).

He, M. et al. Remarkably similar CTLA-4 binding properties of therapeutic ipilimumab and tremelimumab antibodies. Oncotarget 8 , 67129–67139 (2017).

Brahmer, J. R. et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J. Clin. Oncol. 36 , 1714–1768 (2018).

Wang, D. Y. et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 4 , 1721–1728 (2018).

Runcie, K., Budman, D. R., John, V. & Seetharamu, N. Bi-specific and tri-specific antibodies — the next big thing in solid tumor therapeutics. Mol. Med. 24 , 50 (2018).

Bargou, R. et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 321 , 974–977 (2008). This paper describes the first-in-human clinical trial of the CD19-targeting bispecific antibody blinatumomab, which was the first bispecific antibody to achieve widespread adoption in the clinic and subsequently set the stage for the widespread adoption of the bispecific antibody format.

Labrijn, A. F., Janmaat, M. L., Reichert, J. M. & Parren, P. Bispecific antibodies: a mechanistic review of the pipeline. Nat. Rev. Drug Discov. 18 , 585–608 (2019). This detailed review describes the different formats of bispecific antibodies.

Liddy, N. et al. Monoclonal TCR-redirected tumor cell killing. Nat. Med. 18 , 980–987 (2012).

Nathan, P. et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N. Engl. J. Med. 385 , 1196–1206 (2021).

Ahn, M. J. et al. Tarlatamab for patients with previously treated small-cell lung cancer. N. Engl. J. Med. 389 , 2063–2075 (2023).

Park, K. et al. Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study. J. Clin. Oncol. 39 , 3391–3402 (2021).

Moores, S. L. et al. A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors. Cancer Res. 76 , 3942–3953 (2016).

Dixit, S., Abraham, L., Weiser, N. & Gold, M. R. Super-resolution imaging studies of zanidatamab: providing insights into its bispecific mode of action. Cancer Res. 81 , abstr. 1032 (2021).

Article   Google Scholar  

Weiser, N. E. et al. The bispecific antibody zanidatamab’s (ZW25’s) unique mechanisms of action and durable anti-tumor activity in HER2-expressing cancers. Cancer Res . 81 , abstr. 1005 (2021).

Meric-Bernstam, F. et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. Lancet Oncol. 23 , 1558–1570 (2022).

Falchi, L., Vardhana, S. A. & Salles, G. A. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities. Blood 141 , 467–480 (2023).

Tsuchikama, K., Anami, Y., Ha, S. Y. Y. & Yamazaki, C. M. Exploring the next generation of antibody-drug conjugates. Nat. Rev. Clin. Oncol. 21 , 203–223 (2024). This review focuses on the current state and future directions of ADCs in oncology.

Fu, Z., Li, S., Han, S., Shi, C. & Zhang, Y. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduct. Target. Ther. 7 , 93 (2022).

Stapleton, N. M. et al. Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential. Nat. Commun. 2 , 599 (2011).

Natsume, A., Niwa, R. & Satoh, M. Improving effector functions of antibodies for cancer treatment: enhancing ADCC and CDC. Drug Des. Dev. Ther. 3 , 7–16 (2009).

CAS   Google Scholar  

Flygare, J. A., Pillow, T. H. & Aristoff, P. Antibody-drug conjugates for the treatment of cancer. Chem. Biol. Drug Des. 81 , 113–121 (2013).

Hingorani, D. V. et al. Monomethyl auristatin antibody and peptide drug conjugates for trimodal cancer chemo-radio-immunotherapy. Nat. Commun. 13 , 3869 (2022).

Francisco, J. A. et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood 102 , 1458–1465 (2003). This study describes the generation of a CD30-targeting ADC using a peptide cleavable linker. The ADC was later named brentuximab, and it is considered standard first-line therapy for patients with Hodgkin lymphoma and other CD30 + lymphomas. Multiple approved ADCs targeting other cancer antigens now use this drug–linker combination.

Ansell, S. M. et al. Overall survival with brentuximab vedotin in stage III or IV Hodgkin’s lymphoma. N. Engl. J. Med. 387 , 310–320 (2022).

Horwitz, S. et al. The ECHELON-2 trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma. Ann. Oncol. 33 , 288–298 (2022).

Zhang, D. et al. Catalytic cleavage of disulfide bonds in small molecules and linkers of antibody-drug conjugates. Drug Metab. Dispos. 47 , 1156–1163 (2019).

Moore, K. N. et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N. Engl. J. Med. 389 , 2162–2174 (2023).

Kovtun, Y. V. et al. Antibody-drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. Cancer Res. 66 , 3214–3221 (2006).

Oflazoglu, E. et al. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin. Cancer Res. 14 , 6171–6180 (2008).

Conilh, L., Sadilkova, L., Viricel, W. & Dumontet, C. Payload diversification: a key step in the development of antibody-drug conjugates. J. Hematol. Oncol. 16 , 3 (2023).

Ogitani, Y. et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin. Cancer Res. 22 , 5097–5108 (2016). This paper describes the generation of tetrapeptide linker that masks the hydrophobicity of the payload and allows attachment of a large number of hydrophobic payloads without affecting antibody pharmacokinetics. This linker–drug combination is now being used in multiple ADCs that are nearing regulatory approval.

Zammarchi, F. et al. ADCT-402, a PBD dimer-containing antibody drug conjugate targeting CD19-expressing malignancies. Blood 131 , 1094–1105 (2018).

Lewis Phillips, G. D. et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 68 , 9280–9290 (2008).

Cortes, J. et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N. Engl. J. Med. 386 , 1143–1154 (2022). This phase III clinical trial directly compares two HER2-targeting ADCs, showing the benefit of the ADC trastuzumab deruxtecan, which carries the payload DXd attached by a cleavable linker and possesses a high DAR.

Modi, S. et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N. Engl. J. Med. 387 , 9–20 (2022).

Kreitman, R. J. & Pastan, I. Immunotoxins: from design to clinical application. Biomolecules 11 , 1696 (2021).

Li, M., Mei, S., Yang, Y., Shen, Y. & Chen, L. Strategies to mitigate the on- and off-target toxicities of recombinant immunotoxins: an antibody engineering perspective. Antib. Ther. 5 , 164–176 (2022).

Kreitman, R. J. & Pastan, I. Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clin. Cancer Res. 17 , 6398–6405 (2011). This review of immunotoxins shows the development of the first cancer-targeting immunotoxin moxetumomab that received FDA approval for the treatment of hairy cell leukaemia.

Lin, P., Qi, J. & Liu, W. Expert’s views and perspectives: an interview with distinguished investigator Dr. Ira Pastan at the National Cancer Institute at NIH. Antib. Ther. 3 , 163–166 (2020).

Kreitman, R. J. et al. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia 32 , 1768–1777 (2018).

Kreitman, R. J. & Pastan, I. Contextualizing the use of moxetumomab pasudotox in the treatment of relapsed or refractory hairy cell leukemia. Oncologist 25 , e170–e177 (2020).

Kim, Y. S. & Brechbiel, M. W. An overview of targeted alpha therapy. Tumour Biol. 33 , 573–590 (2012).

Parakh, S., Lee, S. T., Gan, H. K. & Scott, A. M. Radiolabeled antibodies for cancer imaging and therapy. Cancers 14 , 1454 (2022).

Witzig, T. E. et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J. Clin. Oncol. 20 , 2453–2463 (2002).

Kaminski, M. S. et al. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin’s lymphomas. J. Clin. Oncol. 19 , 3918–3928 (2001).

Prasad, V. The withdrawal of drugs for commercial reasons: the incomplete story of tositumomab. JAMA Intern. Med. 174 , 1887–1888 (2014).

Alhaj Moustafa, M. et al. Real world long-term follow-up experience with yttrium-90 ibritumomab tiuxetan in previously untreated patients with low-grade follicular lymphoma and marginal zone lymphoma. Clin. Lymphoma Myeloma Leuk. 22 , 618–625 (2022).

Sgouros, G., Bodei, L., McDevitt, M. R. & Nedrow, J. R. Radiopharmaceutical therapy in cancer: clinical advances and challenges. Nat. Rev. Drug Discov. 19 , 589–608 (2020).

Dowden, H. & Munro, J. Trends in clinical success rates and therapeutic focus. Nat. Rev. Drug Discov. 18 , 495–496 (2019).

Wong, C. H., Siah, K. W. & Lo, A. W. Estimation of clinical trial success rates and related parameters. Biostatistics 20 , 273–286 (2019).

Smietana, K., Siatkowski, M. & Moller, M. Trends in clinical success rates. Nat. Rev. Drug Discov. 15 , 379–380 (2016).

Pham, E. et al. Preclinical assessment of a MUC12-targeted BiTE (bispecific T-cell engager) molecule. Mol. Cancer Ther. 20 , 1977–1987 (2021).

Kebenko, M. et al. A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE(R)) antibody construct, in patients with refractory solid tumors. Oncoimmunology 7 , e1450710 (2018).

DeFrancesco, L. Cartography biosciences and nested therapeutics: diamonds in the rough. Nat. Biotechnol. https://doi.org/10.1038/d41587-023-00013-9 (2023).

Mullard, A. Claudin-18.2 attracts the cancer crowd. Nat. Rev. Drug Discov. 22 , 683–686 (2023).

Shah, M. A. et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat. Med. 29 , 2133–2141 (2023).

Janne, P. A. et al. Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated non-small cell lung cancer. Cancer Discov. 12 , 74–89 (2022).

Wainberg, Z. A. et al. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 23 , 1430–1440 (2022).

Paz-Ares, L. et al. Tarlatamab, a first-in-class DLL3-targeted bispecific T-cell engager, in recurrent small-cell lung cancer: an open-label, phase I study. J. Clin. Oncol. 41 , 2893–2903 (2023).

Picozzi, V. et al. Gemcitabine/nab-paclitaxel with pamrevlumab: a novel drug combination and trial design for the treatment of locally advanced pancreatic cancer. ESMO Open 5 , e000668 (2020).

Kelly, W. K. et al. Xaluritamig, a STEAP1 x CD3 XmAb 2+1 immune therapy for metastatic castration-resistant prostate cancer: results from dose exploration in a first-in-human study. Cancer Discov. 14 , 76–89 (2024).

Dannenfelser, R. et al. Discriminatory power of combinatorial antigen recognition in cancer T cell therapies. Cell Syst. 11 , 215–228.e5 (2020).

Kloss, C. C., Condomines, M., Cartellieri, M., Bachmann, M. & Sadelain, M. Combinatorial antigen recognition with balanced signaling promotes selective tumor eradication by engineered T cells. Nat. Biotechnol. 31 , 71–75 (2013).

Banaszek, A. et al. On-target restoration of a split T cell-engaging antibody for precision immunotherapy. Nat. Commun. 10 , 5387 (2019).

Oostindie, S. C. et al. Logic-gated antibody pairs that selectively act on cells co-expressing two antigens. Nat. Biotechnol. 40 , 1509–1519 (2022).

Iozzo, R. V. & Schaefer, L. Proteoglycan form and function: a comprehensive nomenclature of proteoglycans. Matrix Biol. 42 , 11–55 (2015).

Ilieva, K. M. et al. Chondroitin sulfate proteoglycan 4 and its potential as an antibody immunotherapy target across different tumor types. Front Immunol. 8 , 1911 (2018).

Filmus, J., Capurro, M. & Rast, J. Glypicans. Genome Biol. 9 , 224 (2008).

Ho, M. & Kim, H. Glypican-3: a new target for cancer immunotherapy. Eur. J. Cancer 47 , 333–338 (2011).

Li, N., Gao, W., Zhang, Y. F. & Ho, M. Glypicans as cancer therapeutic targets. Trends Cancer 4 , 741–754 (2018).

Li, N. et al. The IgG4 hinge with CD28 transmembrane domain improves V(H)H-based CAR T cells targeting a membrane-distal epitope of GPC1 in pancreatic cancer. Nat. Commun. 14 , 1986 (2023).

Kato, D. et al. GPC1 specific CAR-T cells eradicate established solid tumor without adverse effects and synergize with anti-PD-1 Ab. eLife 9 , e49392 (2020).

Li, N., Fu, H., Hewitt, S. M., Dimitrov, D. S. & Ho, M. Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma. Proc. Natl Acad. Sci. USA 114 , E6623–E6631 (2017).

Bosse, K. R. et al. Identification of GPC2 as an oncoprotein and candidate immunotherapeutic target in high-risk neuroblastoma. Cancer Cell 32 , 295–309.e12 (2017).

Li, N. et al. CAR T cells targeting tumor-associated exons of glypican 2 regress neuroblastoma in mice. Cell Rep. Med. 2 , 100297 (2021).

Phung, Y., Gao, W., Man, Y.-G., Nagata, S. & Ho, M. High-affinity monoclonal antibodies to cell surface tumor antigen glypican-3 generated through a combination of peptide immunization and flow cytometry screening. mAbs 4 , 592–599 (2012).

Li, D. et al. Persistent polyfunctional chimeric antigen receptor T cells that target glypican 3 eliminate orthotopic hepatocellular carcinomas in mice. Gastroenterology 158 , 2250–2265.e20 (2020).

Nakano, K. et al. Anti-glypican 3 antibodies cause ADCC against human hepatocellular carcinoma cells. Biochem. Biophys. Res. Commun. 378 , 279–284 (2009).

Shi, D. et al. Chimeric antigen receptor-glypican-3 T-cell therapy for advanced hepatocellular carcinoma: results of phase I trials. Clin. Cancer Res. 26 , 3979–3989 (2020).

Loffler, A. et al. A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood 95 , 2098–2103 (2000). This paper describes the production of large quantities of a stable bispecific antibody targeting CD19 on B cell lymphomas. The CD19-targeting bispecific antibody was later named blinatumomab and was the first successful bispecific antibody that gained widespread adoption for cancer treatment.

Kantarjian, H. et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N. Engl. J. Med. 376 , 836–847 (2017). This phase III clinical trial establishes the survival benefit of blinatumomab therapy over chemotherapy in patients with ALL.

Maloney, D. G. et al. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood 84 , 2457–2466 (1994).

Coiffier, B. et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N. Engl. J. Med. 346 , 235–242 (2002).

de Weers, M. et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J. Immunol. 186 , 1840–1848 (2011).

Carpenter, R. O. et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin. Cancer Res. 19 , 2048–2060 (2013).

Frerichs, K. A. et al. Preclinical activity of JNJ-7957, a novel BCMAxCD3 bispecific antibody for the treatment of multiple myeloma, is potentiated by daratumumab. Clin. Cancer Res. 26 , 2203–2215 (2020).

Nichakawade, T. D. et al. TRBC1-targeting antibody–drug conjugates for the treatment of T cell cancers. Nature https://doi.org/10.1038/s41586-024-07233-2 (2024).

Paul, S. et al. TCR β chain-directed bispecific antibodies for the treatment of T cell cancers. Sci. Transl. Med . https://doi.org/10.1126/scitranslmed.abd3595 (2021).

Maciocia, P. M. et al. Targeting the T cell receptor β-chain constant region for immunotherapy of T cell malignancies. Nat. Med. 23 , 1416–1423 (2017).

Pearlman, A. H. et al. Targeting public neoantigens for cancer immunotherapy. Nat. Cancer 2 , 487–497 (2021). This review describes the prevalence of targetable public neoantigens in cancer.

Hwang, M. S. et al. Structural engineering of chimeric antigen receptors targeting HLA-restricted neoantigens. Nat. Commun. 12 , 5271 (2021).

Hattori, T. et al. Creating MHC-restricted neoantigens with covalent inhibitors that can be targeted by immune therapy. Cancer Discov. 13 , 132–145 (2023).

Wright, K. M. et al. Hydrophobic interactions dominate the recognition of a KRAS G12V neoantigen. Nat. Commun. 14 , 5063 (2023).

Wu, D., Gallagher, D. T., Gowthaman, R., Pierce, B. G. & Mariuzza, R. A. Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen. Nat. Commun. 11 , 2908 (2020).

Trenevska, I., Li, D. & Banham, A. H. Therapeutic antibodies against intracellular tumor antigens. Front. Immunol. 8 , 1001 (2017).

Hamid, O. et al. 728O results from phase I dose escalation of IMC-F106C, the first PRAME × CD3 ImmTAC bispecific protein in solid tumors. Ann. Oncol. 33 , S875 (2022).

Hofheinz, R. D. et al. Stromal antigen targeting by a humanised monoclonal antibody: an early phase II trial of sibrotuzumab in patients with metastatic colorectal cancer. Onkologie 26 , 44–48 (2003).

Scott, A. M. et al. A phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer. Clin. Cancer Res. 9 , 1639–1647 (2003).

Benson, A. B. III et al. A phase II randomized, double-blind, placebo-controlled study of simtuzumab or placebo in combination with gemcitabine for the first-line treatment of pancreatic adenocarcinoma. Oncologist 22 , 241-e15 (2017).

Hecht, J. R. et al. A phase II, randomized, double-blind, placebo-controlled study of simtuzumab in combination with FOLFIRI for the second-line treatment of metastatic KRAS mutant colorectal adenocarcinoma. Oncologist 22 , 243-e23 (2017).

Bejarano, L., Jordao, M. J. C. & Joyce, J. A. Therapeutic targeting of the tumor microenvironment. Cancer Discov. 11 , 933–959 (2021).

Gomez-Roca, C. et al. Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naive or experienced for immune checkpoint blockade. J. Immunother. Cancer 10 , e004076 (2022).

Ira Seth, W. et al. A phase 1a dose-escalation study of PY159, a monoclonal antibody targeting TREM1 (triggering receptor expressed on myeloid cells 1). J. Clin. Oncol. 41 , 2523 (2023).

Amita P. et al. A phase 1a dose-escalation study of PY314, a TREM2 (triggering receptor expressed on macrophages 2) targeting monoclonal antibody. J. Clin. Oncol . https://doi.org/10.1200/JCO.2022.40.16_suppl.2648 (2022).

Byrne, K. T. & Vonderheide, R. H. CD40 stimulation obviates innate sensors and drives T cell immunity in cancer. Cell Rep. 15 , 2719–2732 (2016).

Byrne, K. T. et al. Neoadjuvant selicrelumab, an agonist CD40 antibody, induces changes in the tumor microenvironment in patients with resectable pancreatic cancer. Clin. Cancer Res. 27 , 4574–4586 (2021).

O’Hara, M. H. et al. CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. Lancet Oncol. 22 , 118–131 (2021).

Curigliano, G. et al. Phase I/Ib clinical trial of sabatolimab, an anti-TIM-3 antibody, alone and in combination with spartalizumab, an anti-PD-1 antibody, in advanced solid tumors. Clin. Cancer Res. 27 , 3620–3629 (2021).

Kim, H. R. et al. Cobolimab with dostarlimab and docetaxel in patients with advanced non-small cell lung cancer (NSCLC): COSTAR lung. J. Thorac. Oncol . https://doi.org/10.1016/j.jtho.2022.07.183 (2022).

Spiegel, J. Y. et al. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat. Med. 27 , 1419–1431 (2021).

Bluhm, J. et al. CAR T cells with enhanced sensitivity to B cell maturation antigen for the targeting of B cell non-Hodgkin’s lymphoma and multiple myeloma. Mol. Ther. 26 , 1906–1920 (2018).

Friedman, K. M. et al. Effective targeting of multiple B-cell maturation antigen-expressing hematological malignances by anti-B-cell maturation antigen chimeric antigen receptor T cells. Hum. Gene Ther. 29 , 585–601 (2018).

Golay, J. et al. CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59. Blood 98 , 3383–3389 (2001).

Teeling, J. L. et al. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J. Immunol. 177 , 362–371 (2006).

Perez, H. L. et al. Antibody-drug conjugates: current status and future directions. Drug Discov. Today 19 , 869–881 (2014).

Sharma, P. & Kranz, D. M. Recent advances in T-cell engineering for use in immunotherapy. F1000Res https://doi.org/10.12688/f1000research.9073.1 (2016).

Cancer Research Institute. Approval timeline of active immunotherapies. Cancer Research Institute https://www.cancerresearch.org/regulatory-approval-timeline-of-active-immunotherapies (2024).

Johnson, P. C., Gainor, J. F., Sullivan, R. J., Longo, D. L. & Chabner, B. Immune checkpoint inhibitors — the need for innovation. N. Engl. J. Med. 388 , 1529–1532 (2023).

Revisiting checkpoint blockade. Nat. Biotechnol . 40 , 981 (2022).

Postel-Vinay, S. et al. First-in-human phase I study of the OX40 agonist GSK3174998 with or without pembrolizumab in patients with selected advanced solid tumors (ENGAGE-1). J. Immunother. Cancer 11 , e005301 (2023).

Davis, E. J. et al. First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors. J. Immunother. Cancer 10 , e004235 (2022).

Andre, P. et al. Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells. Cell 175 , 1731–1743.e13 (2018).

Qin, S. et al. Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4. Mol. Cancer 18 , 155 (2019).

Tawbi, H. A. et al. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. N. Engl. J. Med. 386 , 24–34 (2022).

Gilead. Gilead statement on the discontinuation of magrolimab study in AML with TP53 mutations. Gilead https://www.gilead.com/news-and-press/company-statements/gilead-statement-on-the-discontinuation-of-magrolimab-study-in-aml-with-tp53-mutations (2023).

Gilead. Gilead to discontinue phase 3 ENHANCE study of magrolimab plus azacitidine in higher-risk MDS. Gilead https://www.gilead.com/news-and-press/press-room/press-releases/2023/7/gilead-to-discontinue-phase-3-enhance-study-of-magrolimab-plus-azacitidine-in-higher-risk-mds (2023).

Zhao, B., Zhao, H. & Zhao, J. Efficacy of PD-1/PD-L1 blockade monotherapy in clinical trials. Ther. Adv. Med. Oncol. 12 , 1758835920937612 (2020).

Johnson, D. B., Nebhan, C. A., Moslehi, J. J. & Balko, J. M. Immune-checkpoint inhibitors: long-term implications of toxicity. Nat. Rev. Clin. Oncol. 19 , 254–267 (2022).

Ying Cheng et al. Phase I/II combination study of tifcemalimab with toripalimab in patients with refractory extensive stage small cell lung cancer (ES-SCLC). J. Clin. Oncol. 41 , 8579 (2023).

Shenderov, E. et al. Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial. Nat. Med. 29 , 888–897 (2023).

Ansell, S. M. et al. Safety and activity of varlilumab, a novel and first-in-class agonist anti-CD27 antibody, for hematologic malignancies. Blood Adv. 4 , 1917–1926 (2020).

Claus, C., Ferrara-Koller, C. & Klein, C. The emerging landscape of novel 4-1BB (CD137) agonistic drugs for cancer immunotherapy. MAbs 15 , 2167189 (2023).

Elizabeth Budde, M. et al. Preliminary results of a phase 1 dose escalation study of the first-in-class IgM based bispecific antibody Igm-2323 (anti-CD20 x anti-CD3) in patients with advanced B-cell malignancies. Blood 136 , 45–46 (2020).

Wang, B. T. et al. Multimeric anti-DR5 IgM agonist antibody IGM-8444 is a potent inducer of cancer cell apoptosis and synergizes with chemotherapy and BCL-2 inhibitor ABT-199. Mol. Cancer Ther. 20 , 2483–2494 (2021).

Li, K., Yun, R., Chai, M., Yakkundi, P. & Rosete, R. Novel CD38xCD3 bispecific IgM T cell engager, IGM-2644, potently kills multiple myeloma cells though complement and T cell dependent mechanisms. Cancer Res. 83 , 2959 (2023).

Wang, B. et al. Anti-DR5 agonist IgM antibody IGM-8444 combined with SMAC mimetic birinapant induces strong synergistic tumor cytotoxicity. Cancer Res. 82 , 1068 (2022).

Klein, C., Brinkmann, U., Reichert, J. M. & Kontermann, R. E. The present and future of bispecific antibodies for cancer therapy. Nat. Rev. Drug Discov. https://doi.org/10.1038/s41573-024-00896-6 (2024). This review focuses on the current state and future directions of bispecific antibodies in oncology.

Dickinson, M. J. et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N. Engl. J. Med. 387 , 2220–2231 (2022).

Bacac, M. et al. CD20-TCB with obinutuzumab pretreatment as next-generation treatment of hematologic malignancies. Clin. Cancer Res. 24 , 4785–4797 (2018).

Nolan-Stevaux, O. et al. AMG 509 (xaluritamig), an anti-STEAP1 XmAb 2+1 T-cell redirecting immune therapy with avidity-dependent activity against prostate cancer. Cancer Discov. 14 , 90–103 (2024).

Li, G. et al. Novel CD123xCD3 bispecific IgM antibody, IGM-2537, potently induces T-cell mediated cytotoxicity of acute myeloid leukemia cells with minimal cytokine release. Cancer Res. 83 , 2933 (2023).

Genevive, H. H. et al. Pharmacodynamics and biomarker correlates of imvotamab (IGM-2323), the first-in-class CD20xCD3 bispecific IgM antibody with dual mechanisms of action, in patients with advanced B cell malignancies. Blood 140 , 6436–6438 (2022).

Luke, J. J. et al. The PD-1- and LAG-3-targeting bispecific molecule tebotelimab in solid tumors and hematologic cancers: a phase 1 trial. Nat. Med. 29 , 2814–2824 (2023).

Dovedi, S. J. et al. Design and efficacy of a monovalent bispecific PD-1/CTLA4 antibody that enhances CTLA4 blockade on PD-1 + activated T cells. Cancer Discov. 11 , 1100–1117 (2021).

Gao, X. et al. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. Lancet Oncol. 24 , 1134–1146 (2023).

Chen, B. et al. A phase Ib/II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) plus anlotinib as first-line treatment in patients with advanced non-small cell lung cancer. Br. J. Cancer 130 , 450–456 (2024).

Li, Q. et al. The anti-PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel in first-line treatment of metastatic triple-negative breast cancer: a multicenter phase II trial. Nat. Commun. 15 , 1015 (2024).

Kvarnhammar, A. M. et al. The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation. J. Immunother. Cancer 7 , 103 (2019).

Karin Lee et al. Preclinical studies support clinical development of AZD2936, a monovalent bispecific humanized antibody targeting PD-1 and TIGIT. J. Immunother. Cancer 10 , A489 (2023).

Google Scholar  

Shapir Itai, Y. et al. Bispecific dendritic-T cell engager potentiates anti-tumor immunity. Cell 187 , 375–389.e18 (2024).

Zhao, L. et al. A novel CD19/CD22/CD3 trispecific antibody enhances therapeutic efficacy and overcomes immune escape against B-ALL. Blood 140 , 1790–1802 (2022).

Wu, L. et al. Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation. Nat. Cancer 1 , 86–98 (2020).

Pardon, E. et al. A general protocol for the generation of nanobodies for structural biology. Nat. Protoc. 9 , 674–693 (2014).

Li, D. et al. Camel nanobody-based B7-H3 CAR-T cells show high efficacy against large solid tumours. Nat. Commun. 14 , 5920 (2023).

Xu, J. et al. Nanobodies from camelid mice and llamas neutralize SARS-CoV-2 variants. Nature 595 , 278–282 (2021). This paper describes the generation of a transgenic mouse (nanomouse), which expresses camelid variable heavy domain of heavy chain (VHH) genes. Such transgenic mouse platforms enable the production of nanobodies from mice.

Hu, Y. et al. RenNano® mice: a heavy-chain-only antibody platform for the generation of nanobody therapeutics. Cancer Res. 83 , LB210 (2023).

De Genst, E. et al. Molecular basis for the preferential cleft recognition by dromedary heavy-chain antibodies. Proc. Natl Acad. Sci. USA 103 , 4586–4591 (2006).

Berdeja, J. G. et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet 398 , 314–324 (2021).

Munshi, N. C. et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N. Engl. J. Med. 384 , 705–716 (2021).

Jovcevska, I. & Muyldermans, S. The therapeutic potential of nanobodies. BioDrugs 34 , 11–26 (2020).

Lucchi, R., Bentanachs, J. & Oller-Salvia, B. The masking game: design of activatable antibodies and mimetics for selective therapeutics and cell control. ACS Cent. Sci. 7 , 724–738 (2021). This review describes the recent advancements in activatable antibodies in cancer and other diseases.

Sulea, T. et al. Structure-based engineering of pH-dependent antibody binding for selective targeting of solid-tumor microenvironment. MAbs 12 , 1682866 (2020).

Kang, J. C. et al. Engineering a HER2-specific antibody-drug conjugate to increase lysosomal delivery and therapeutic efficacy. Nat. Biotechnol. 37 , 523–526 (2019).

Zhang, Y. et al. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy. Cell Res. 29 , 609–627 (2019).

Desnoyers, L. R. et al. Tumor-specific activation of an EGFR-targeting probody enhances therapeutic index. Sci. Transl. Med. 5 , 207ra144 (2013).

Autio, K. A., Boni, V., Humphrey, R. W. & Naing, A. Probody therapeutics: an emerging class of therapies designed to enhance on-target effects with reduced off-tumor toxicity for use in immuno-oncology. Clin. Cancer Res. 26 , 984–989 (2020).

Boni, V. et al. Praluzatamab ravtansine, a CD166-targeting antibody-drug conjugate, in patients with advanced solid tumors: an open-label phase I/II Trial. Clin. Cancer Res. 28 , 2020–2029 (2022).

Boustany, L. M. et al. A probody T cell-engaging bispecific antibody targeting EGFR and CD3 inhibits colon cancer growth with limited toxicity. Cancer Res. 82 , 4288–4298 (2022).

Lajoie, M. J. et al. Designed protein logic to target cells with precise combinations of surface antigens. Science 369 , 1637–1643 (2020).

Xu, S. Internalization, trafficking, intracellular processing and actions of antibody-drug conjugates. Pharm. Res. 32 , 3577–3583 (2015).

Saunders, K. O. Conceptual approaches to modulating antibody effector functions and circulation half-life. Front. Immunol. 10 , 1296 (2019).

Brandl, F., Busslinger, S., Zangemeister-Wittke, U. & Pluckthun, A. Optimizing the anti-tumor efficacy of protein-drug conjugates by engineering the molecular size and half-life. J. Control. Release 327 , 186–197 (2020).

Bardia, A. et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N. Engl. J. Med. 384 , 1529–1541 (2021).

Senior, M. Cancer-targeting antibody-drug conjugates drive dealmaking frenzy. Nat. Biotechnol. 42 , 362–366 (2024).

Weng, W. et al. Antibody-exatecan conjugates with a novel self-immolative moiety overcome resistance in colon and lung cancer. Cancer Discov. 13 , 950–973 (2023).

Li, B. T. et al. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N. Engl. J. Med. 386 , 241–251 (2022).

Siena, S. et al. Trastuzumab deruxtecan (DS-8201) in patients with HER2-expressing metastatic colorectal cancer (DESTINY-CRC01): a multicentre, open-label, phase 2 trial. Lancet Oncol. 22 , 779–789 (2021).

Esfandiari, A., Cassidy, S. & Webster, R. M. Bispecific antibodies in oncology. Nat. Rev. Drug Discov. 21 , 411–412 (2022).

do Pazo, C., Nawaz, K. & Webster, R. M. The oncology market for antibody-drug conjugates. Nat. Rev. Drug Discov. 20 , 583–584 (2021).

Criscitiello, C., Morganti, S. & Curigliano, G. Antibody-drug conjugates in solid tumors: a look into novel targets. J. Hematol. Oncol. 14 , 20 (2021).

Michael, L. W. et al. Zilovertamab vedotin targeting of ROR1 as therapy for lymphoid cancers. NEJM Evid. https://doi.org/10.1056/EVIDoa2100001 (2021).

Saura Manich, C. et al. LBA15 — primary outcome of the phase III SYD985.002/TULIP trial comparing [vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER2-positive locally advanced or metastatic breast cancer. Ann. Oncol. 32 , S1283–S1346 (2021).

Powles, T. B. et al. LBA6 EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). Ann. Oncol. 34 , S1340 (2023).

Antignani, A. et al. Targeting receptors on cancer cells with protein toxins. Biomolecules https://doi.org/10.3390/biom10091331 (2020).

Pemmaraju, N. et al. Tagraxofusp in blastic plasmacytoid dendritic-cell neoplasm. N. Engl. J. Med. 380 , 1628–1637 (2019).

Saleh, M. N. et al. Antitumor activity of DAB389IL-2 fusion toxin in mycosis fungoides. J. Am. Acad. Dermatol. 39 , 63–73 (1998).

Sartor, O. et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N. Engl. J. Med. 385 , 1091–1103 (2021).

Strosberg, J. et al. Phase 3 trial of (177)Lu-dotatate for midgut neuroendocrine tumors. N. Engl. J. Med. 376 , 125–135 (2017).

Michael, S. H. et al. First-in-human safety, imaging and dosimetry of [68Ga]Ga-DPI-4452, a novel CA IX-targeting peptide, in patients with clear cell renal cell carcinoma. J. Clin. Oncol . https://doi.org/10.1200/JCO.2024.42.4_suppl.37 (2024).

Dolgin, E. Radioactive drugs emerge from the shadows to storm the market. Nat. Biotechnol. 36 , 1125–1127 (2018).

Sathekge, M. M. et al. Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study. Lancet Oncol. 25 , 175–183 (2024).

Slamon, D. J. et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235 , 177–182 (1987).

Rubin, I. & Yarden, Y. The basic biology of HER2. Ann. Oncol. 12 , S3-8 (2001).

Verma, S. et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 367 , 1783–1791 (2012).

Morgan, R. A. et al. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther. 18 , 843–851 (2010).

Saunders, L. R. et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci. Transl. Med. 7 , 302ra136 (2015).

Vos, J. L. et al. Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma. Nat. Commun. 12 , 7348 (2021).

Download references

Acknowledgements

S.P. M.F.K., C.B., N.P. and S.Z. were supported by The Virginia and D.K. Ludwig Fund for Cancer Research, the Lustgarten Foundation for Pancreatic Cancer Research, The Commonwealth Fund, the Bloomberg~Kimmel Institute for Cancer Immunotherapy, and the National Institutes of Health (NIH) Cancer Center Support grant P30 CA006973. S.P. was supported by NCI grant K08CA270403, the Leukaemia Lymphoma Society Translation Research Program award, the American Society of Hematology Scholar award, and the Swim Across America Translational Cancer Research Award. M.F.K. was supported by NIH/NIAID grant 1R21AI176764-01, the Jerome Greene Foundation, the Cupid Foundation, the Lupus Research Alliance Lupus Innovation Award, the Rheumatology Research Foundation Investigator Award, the Harrington Discovery Institute Harrington Scholar-Innovator Award, the Sol Goldman MS Research Program, and the Bisciotti Foundation Translational Fund. C.B. was supported by NCI grant R37 CA230400. M.H. was supported by the Intramural Research Program of NIH, NCI and Center for Cancer Research (Z01 BC010891, ZIA BC010891 and ZIC BC 011891).

Author information

Authors and affiliations.

Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA

Suman Paul, Drew M. Pardoll, Nickolas Papadopoulos & Shibin Zhou

Division of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Maximilian F. Konig

Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

Chetan Bettegowda

Discovery Chemistry, Merck Research Laboratory, Merck and Co, West Point, PA, USA

Katharine M. Wright & Sandra B. Gabelli

Antibody Engineering Program, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

Mitchell Ho

Third Rock Ventures, San Francisco, CA, USA

Andrea van Elsas

You can also search for this author in PubMed   Google Scholar

Contributions

S.P., K.M.W., S.B.G. and M.H. researched data for the article. S.P., S.B.G., M.H. and A.vE. contributed substantially to discussion of the content. S.P., K.M.W., S.B.G., M.H., A.vE. and S.Z. wrote the article. All authors reviewed and/or edited the manuscript before submission.

Corresponding authors

Correspondence to Suman Paul , Sandra B. Gabelli , Mitchell Ho or Andrea van Elsas .

Ethics declarations

Competing interests.

The Johns Hopkins University has filed patent applications related to technologies described in this paper on which S.P., M.F.K., N.P., D.M.P. and S.Z. are listed as inventors. M.H. is an inventor on NIH patents in antibody and cell therapies and may receive blinded royalties from the NIH. N.P. is a founder of Thrive Earlier Detection, an Exact Sciences company. N.P. is a consultant to Thrive Earlier Detection. N.P. and S.Z. hold equity in Exact Sciences. N.P. and S.Z. are founders of and/or consultants to and own equity in ManaT Bio., Neophore and Personal Genome Diagnostics. N.P. holds equity in Haystack Oncology and CAGE Pharma. N.P. is a consultant to Vidium. S.P. owns equity in Gilead, is a consultant to Merck and received payment from IQVIA. M.F.K. is a consultant to Argenx, Atara Biotherapeutics, Revel Pharmaceuticals, Sana Biotechnology and Sanofi. S.Z. has a research agreement with BioMed Valley Discoveries, Inc. C.B. is a consultant for Depuy-Synthes, Bionaut Labs, Galectin Therapeutics, Haystack Oncology and Privo Technologies. C.B. is a co-founder of OrisDx and Belay Diagnostics. D.M.P. reports grant and patent royalties through institution from BMS, a grant from Compugen, stock from Trieza Therapeutics and Dracen Pharmaceuticals, and founder equity from Potenza; is a founder of and consultant to and owns equity in ManaT Bio; is a consultant for Aduro Biotech, Amgen, Astra Zeneca (Medimmune/Amplimmune), Bayer, DNAtrix, Dynavax Technologies Corporation, Ervaxx, FLX Bio, Rock Springs Capital, Janssen, Merck, Tizona and Immunomic-Therapeutics; is on the scientific advisory board of Five Prime Therapeutics, Camden Nexus II, WindMil; and is on the board of directors for Dracen Pharmaceuticals. K.M.W. and S.B.G. are employees of Merck & Co., Inc. at the time of submission and may have stock ownership in Merck & Co., Inc., Rahway, NJ, USA.

Peer review

Peer review information.

Nature Reviews Cancer thanks Falk Nimmerjahn and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

American Cancer Society: https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2023-cancer-facts-figures.html

Antibody Society: https://www.antibodysociety.org/resources/approved-antibodies/

Supplementary information

Supplementary information.

A severe and potentially life-threatening reaction owing to exposure to an allergen such as an antibody or other medication. Common symptoms of anaphylaxis include swelling of the face and throat, difficulty in breathing, an increase in heart rate, a drop in blood pressure and loss of consciousness.

(ADCC). A mechanism through which antibodies bind to target cells followed by recruitment of immune cells such as NK cells and macrophages to kill the target cells. The immune cells secrete cytotoxic granules (perforins and granzymes), and induce FAS signalling leading to target cell death.

(ADCP). A mechanism through which antibodies bind to target cells, which in turn stimulates immune cells such as macrophages to engulf and degrade the target cells.

Isolation and expansion of single B cells that produce the desired monoclonal antibodies, to obtain the antibody-coding sequence.

With antibody–drug conjugates (ADCs), refers to a phenomenon wherein neighbouring cells near the target cancer cell are killed by the released cytotoxic payload. This effect can enhance the overall potency of the ADC by causing a broader destruction of cancer cells beyond the primary target cell.

Condition characterized by the leakage of fluid from small blood vessels (capillaries) into surrounding tissues. This leakage leads to a decrease in blood volume and can result in low blood pressure along with oedema (swelling) in various parts of the body, including the lungs, and organ failure.

(CDRs). Specific regions within the antibody heavy and light chain variable domains that bind to the target antigen.

(CDC). A mechanism through which antibodies bind to the target cell followed by activation of the complement system, leading to lysis of the target cells.

(CRS). Systemic inflammation characterized by a constellation of symptoms such as fever, hypotension and hypoxia and mediated by the release of multiple cytokines from the immune cells of patients. CRS is a typical adverse effect observed with the use of T cell engager (TCE) bispecific antibodies.

A reduction in the number of circulating blood cells, such as red blood cells (erythrocytes), white blood cells (leukocytes) and/or platelets (thrombocytes). Cytopenias can be caused by several factors including exposure to drugs or antibodies that hinder the growth of new cells.

(DAR). The number of drugs attached to each antibody in an ADC.

(Fab). An antibody which consists of two identical Fab fragments and one Fc fragment. Each Fab fragment is responsible for binding to a specific antigen. The Fab fragment is obtained by cleaving the antibody at specific sites using enzymes, such as papain or pepsin.

(Fc). Fc fragment interacts with various immune cells through Fc receptors and with complement proteins that contribute to the immune response generated by the antibody. Each antibody class and subclass has unique Fc regions. Understanding the Fc fragment is crucial in the design of therapeutic antibodies because modifications to this region can impact the pharmacokinetics, effector functions and therapeutic efficacy of an antibody.

A rare but serious condition that is characterized by the combination of haemolytic anaemia (destruction of red blood cells), thrombocytopenia (low platelet count) and acute kidney injury. It can be mediated by bacterial infections (such as Escherischia coli ) or exposure to drugs and antibodies.

Refers to the property of being repelled by water. Hydrophobic substances are insoluble or poorly soluble in water. The hydrophobicity of the payload can affect the overall stability of the ADC. Highly hydrophobic payloads may lead to aggregation or destabilization of the ADC structure, potentially impacting its efficacy and safety.

(MSI-H). Cells with mismatch-repair deficiency resulting in high mutation burden and altered microsatellite (tract of repetitive DNA) sequences. MSI-H cancers are associated with a higher response to immune checkpoint-inhibiting antibodies.

Identical antibodies that bind to a specific part of the target antigen (epitope) and are derived from single clones of immune cells (such as B cells, plasma cells or hybridoma cells).

A group of disorders characterized by abnormal production and maturation of blood cells in the bone marrow. In myelodysplastic syndromes, the bone marrow fails to produce enough healthy blood cells, leading to low levels of red blood cells (anaemia), white blood cells (leukopenia) and platelets (thrombocytopenia).

(FcRn). A receptor expressed by vascular endothelial cells and immune cells, which binds to the Fc portion of IgG antibodies. IgG antibody binding to FcRn leads to receptor-mediated internalization and recycling of the IgG, which is responsible for the long IgG half-life (about 21 days) in circulation.

A potential side effect that can occur owing to the cytotoxic payload component of the ADC affecting the peripheral nerves. Peripheral neuropathy caused by ADCs can manifest as numbness, tingling, burning sensations or pain in the hands, feet or other extremities.

A public neoantigen is derived from a mutated protein and is found in multiple individuals with the same type of cancer. This shared characteristic makes public neoantigens particularly important in cancer immunotherapy because therapies targeting these common neoantigens can benefit a broad patient population. Common public neoantigens include BRAF V600E , KRAS G12D , KRAS G12C and TP53 R175H . By contrast, private neoantigens are unique to an individual patient with cancer. Targeting private neoantigens requires the development of personalized therapies such as custom cancer vaccines and T cell-based therapies.

(scFv). An engineered antibody fragment composed of variable regions of the heavy and light chains combined into a single peptide chain by a linker. The scFv retains the ability to bind specifically to a target antigen, similar to a full-size antibody. The advantages of scFv include its smaller size (~25 kDa), which facilitates easier production and manipulation.

Also known as nanobodies, are antibodies derived from camelids that consist of only a variable heavy domain and as a result have a relatively low molecular weight (~15 kDa), hence the name nanobody. By contrast, human antibodies consist of variable heavy and light domains and have higher molecular weights (a full-length IgG antibody is ~150 kDa and an scFv is ~ 25 kDa).

Enzymes that maintain proper function and stability of DNA by cleaving DNA to relieve torsional strain and supercoiling occurring owing to processes such as DNA replication. Topoisomerase inhibitors disrupt this ability to maintain DNA and cause cell death.

Proteins and other antigenic molecules expressed on the surface of tumour cells that can be targeted by therapeutic antibodies.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Cite this article.

Paul, S., Konig, M.F., Pardoll, D.M. et al. Cancer therapy with antibodies. Nat Rev Cancer (2024). https://doi.org/10.1038/s41568-024-00690-x

Download citation

Accepted : 29 March 2024

Published : 13 May 2024

DOI : https://doi.org/10.1038/s41568-024-00690-x

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.