Milestones in Cancer Research and Discovery

During the past 250 years, we have witnessed many landmark discoveries in our efforts to make progress against cancer, an affliction known to humanity for thousands of years. This timeline shows a few key milestones in the history of cancer research.

1775: Chimney Soot & Squamous Cell Carcinoma

Percivall Pott identifies a relationship between exposure to chimney soot and the incidence of squamous cell carcinoma of the scrotum among chimney sweeps. His report is the first to clearly link an environmental exposure to the development of cancer.

1863: Inflammation & Cancer

Rudolph Virchow identifies white blood cells (leukocytes) in cancerous tissue, making the first connection between inflammation and cancer. Virchow also coins the term “leukemia” and is the first person to describe the excess number of white blood cells in the blood of patients with this disease.

1882: The First Radical Mastectomy to Treat Breast Cancer

William Halsted performs the first radical mastectomy to treat breast cancer. This surgical procedure remains the standard operation for breast cancer until the latter half of the 20th century.

1886: Inheritance of Cancer Risk

Brazilian ophthalmologist Hilário de Gouvêa provides the first documented evidence that a susceptibility to cancer can be passed on from a parent to a child. He reports that two of seven children born to a father who was successfully treated for childhood retinoblastoma, a malignant tumor of the eye, also developed the disease.

1895: The First X-Ray

Wilhelm Roentgen discovers x-rays. The first x-ray picture is an image of his wife’s hand.

1898: Radium & Polonium

Marie and Pierre Curie discover the radioactive elements radium and polonium. Within a few years, the use of radium in cancer treatment begins.

1902: Cancer Tumors & Single Cells with Chromosome Damage

Theodor Boveri proposes that cancerous tumors arise from single cells that have experienced chromosome damage and suggests that chromosome alterations cause the cells to divide uncontrollably.

1903: The First Use of Radiation Therapy to Cure Cancer

S.W. Goldberg and Efim London describe the use of radium to treat two patients with basal cell carcinoma of the skin. The disease was eradicated in both patients.

1909: Immune Surveillance

Paul Ehrlich proposes that the immune system usually suppresses tumor formation, a concept that becomes known as the “immune surveillance” hypothesis. This proposal prompts research, which continues today, to harness the power of the immune system to fight cancer.

1911: Cancer in Chickens

Peyton Rous discovers a virus that causes cancer in chickens (Rous sarcoma virus), establishing that some cancers are caused by infectious agents.

1915: Cancer in Rabbits

Katsusaburo Yamagiwa and Koichi Ichikawa induce cancer in rabbits by applying coal tar to their skin, providing experimental proof that chemicals can cause cancer.

1928: The Pap Smear

George Papanicolaou discovers that cervical cancer can be detected by examining cells from the vagina under a microscope. This breakthrough leads to the development of the Pap test, which allows abnormal cervical cells to be detected and removed before they become cancerous.

1932: The Modified Radical Mastectomy for Breast Cancer

David H. Patey develops the modified radical mastectomy for breast cancer. This surgical procedure is less disfiguring than the radical mastectomy and eventually replaces it as the standard surgical treatment for breast cancer.

1937: The National Cancer Institute (NCI)

Legislation signed by President Franklin D. Roosevelt establishes the National Cancer Institute (NCI).

1937: Breast-Sparing Surgery Followed by Radiation

Sir Geoffrey Keynes describes the treatment of breast cancer with breast-sparing surgery followed by radiation therapy. After surgery to remove the tumor, long needles containing radium are inserted throughout the affected breast and near the adjacent axillary lymph nodes.

1941: Hormonal Therapy

Charles Huggins discovers that removing the testicles to lower testosterone production or administering estrogens causes prostate tumors to regress. Such hormonal manipulation—more commonly known as hormonal therapy—continues to be a mainstay of prostate cancer treatment.

1947: Antimetabolites

Sidney Farber shows that treatment with the antimetabolite drug aminopterin, a derivative of folic acid, induces temporary remissions in children with acute leukemia. Antimetabolite drugs are structurally similar to chemicals needed for important cellular processes, such as DNA synthesis, and cause cell death by blocking those processes.

1949: Nitrogen Mustard

The Food and Drug Administration (FDA) approves nitrogen mustard (mechlorethamine) for the treatment of cancer. Nitrogen mustard belongs to a class of drugs called alkylating agents, which kill cells by chemically modifying their DNA.

1950: Cigarette Smoking & Lung Cancer

Ernst Wynder, Evarts Graham, and Richard Doll identify cigarette smoking as an important factor in the development of lung cancer.

1953: The First Complete Cure of a Human Solid Tumor

Roy Hertz and Min Chiu Li achieve the first complete cure of a human solid tumor by chemotherapy when they use the drug methotrexate to treat a patient with choriocarcinoma, a rare cancer of the reproductive tissue that mainly affects women.

1958: Combination Chemotherapy

NCI researchers Emil Frei, Emil Freireich, and James Holland and their colleagues demonstrate that combination chemotherapy with the drugs 6-mercaptopurine and methotrexate can induce partial and complete remissions and prolong survival in children and adults with acute leukemia.

1960: The Philadelphia Chromosome

Peter Nowell and David Hungerford describe an unusually small chromosome in the cancer cells of patients with chronic myelogenous leukemia (CML). This chromosome, which becomes known as the Philadelphia chromosome, is found in the leukemia cells of 95% of patients with CML.

1964: A Focus on Cigarette Smoking

The U.S. Surgeon General issues a report stating that cigarette smoking is an important health hazard in the United States and that action is required to reduce its harmful effects.

1964: The Epstein-Barr virus

For the first time, a virus—the Epstein-Barr virus (EBV)—is linked to a human cancer (Burkitt lymphoma). EBV is later shown to cause several other cancers, including nasopharyngeal carcinoma, Hodgkin lymphoma, and some gastric (stomach) cancers.

1971: The National Cancer Act

On December 23, President Richard M. Nixon signs the National Cancer Act, which authorizes the NCI Director to coordinate all activities of the National Cancer Program, establish national cancer research centers, and establish national cancer control programs.

1976: The DNA of Normal Chicken Cells

Dominique Stehelin, Harold Varmus, J. Michael Bishop, and Peter Vogt discover that the DNA of normal chicken cells contains a gene related to the oncogene (cancer-causing gene) of avian sarcoma virus, which causes cancer in chickens. This finding eventually leads to the discovery of human oncogenes.

1978: Tamoxifen

FDA approves tamoxifen, an antiestrogen drug originally developed as a birth control treatment, for the treatment of breast cancer. Tamoxifen represents the first of a class of drugs known as selective estrogen receptor modulators, or SERMs, to be approved for cancer therapy.

1979: The TP53 Gene

The TP53 gene (also called p53), the most commonly mutated gene in human cancer, is discovered. It is a tumor suppressor gene, meaning its protein product (p53 protein) helps control cell proliferation and suppress tumor growth.

1984: HER2 Gene Discovered

Researchers discover a new oncogene in rat cells that they call “neu.” The human version of this gene, called HER2 (and ErbB2), is overexpressed in about 20% to 25% of breast cancers (known as HER2-positive breast cancers) and is associated with more aggressive disease and a poor prognosis.

1984: HPV 16 & 18

DNA from human papillomavirus (HPV) types 16 and 18 is identified in a large percentage of cervical cancers, establishing a link between infection with these HPV types and cervical carcinogenesis.

1985: Breast-Conserving Surgery

Results from an NCI-supported clinical trial show that women with early-stage breast cancer who were treated with breast-conserving surgery (lumpectomy) followed by whole-breast radiation therapy had similar rates of overall survival and disease-free survival as women who were treated with mastectomy alone.

1986: HER2 Oncogene Cloning

The human oncogene HER2 (also called neu and erbB2) is cloned. Overexpression of the protein product of this gene, which occurs in about 20% to 25% of breast cancers (known as HER2-positive breast cancers), is associated with more aggressive disease and a poor prognosis.

1993: Guaiac Fecal Occult Blood Testing (FOBT)

Results from an NCI-supported clinical trial show that annual screening with guaiac fecal occult blood testing (FOBT) can reduce colorectal cancer mortality by about 33%.

1994: BRCA1 Tumor Suppressor Gene Cloning

The tumor suppressor gene BRCA1 is cloned. Specific inherited mutations in this gene greatly increase the risks of breast and ovarian cancer in women and the risks of several other cancers in both men and women.

1995: BRCA2 Tumor Suppressor Gene Cloning

The tumor suppressor gene BRCA2 is cloned. Similar to BRCA1, inheriting specific BRCA2 gene mutations greatly increases the risks of breast and ovarian cancer in women and the risks of several other cancers in both men and women.

1996: Anastrozole

FDA approves anastrozole for the treatment of estrogen receptor-positive advanced breast cancer in postmenopausal women. Anastrozole is the first aromatase inhibitor (a drug that blocks the production of estrogen in the body) to be approved for cancer therapy.

1997: Rituximab

FDA approves rituximab, a monoclonal antibody, for use in patients with treatment-resistant, low-grade or follicular B-cell non-Hodgkin lymphoma (NHL). Rituximab is the first monoclonal antibody approved for use in cancer therapy. It is later approved as an initial treatment for these types of NHL, for another type of NHL called diffuse large B-cell lymphoma, and for chronic lymphocytic leukemia.

1998: NCI-Sponsored Breast Cancer Prevention Trial

Results of the NCI-sponsored Breast Cancer Prevention Trial show that the antiestrogen drug tamoxifen can reduce the incidence of breast cancer among women who are at increased risk of the disease by about 50%. FDA approves tamoxifen to reduce the incidence of breast cancer in women at increased risk.

1998: Trastuzumab

FDA approves trastuzumab, a monoclonal antibody that targets cancer cells that overexpress the HER2 gene, for the treatment of women with HER2-positive metastatic breast cancer. Trastuzumab is later approved for the adjuvant (post-operative) treatment of women with HER2-positive early-stage breast cancer.

2001: Imatinib Mesylate

Results of a clinical trial show that the drug imatinib mesylate, which targets a unique protein produced by the Philadelphia chromosome, is effective against chronic myelogenous leukemia (CML). Imatinib treatment changes the usually fatal disease into a manageable condition. Later, it is also shown to be effective in the treatment of gastrointestinal stromal tumors (GIST).

2003: NCI-Sponsored Prostate Cancer Prevention Trial (PCPT)

Results of the NCI-sponsored Prostate Cancer Prevention Trial (PCPT) show that the drug finasteride, which reduces the production of male hormones in the body, lowers a man’s risk of prostate cancer by about 25%.

2006: NCI’s Study of Tamoxifen and Raloxifene (STAR)

Results of NCI’s Study of Tamoxifen and Raloxifene (STAR) show that postmenopausal women at increased risk of breast cancer can reduce their risk of developing the disease if they take the antiestrogen drug raloxifene. The risk of serious side effects is lower with raloxifene than with tamoxifen.

2006: Gardasil

FDA approves the human papillomavirus (HPV) vaccine Gardasil, which protects against infection by the two HPV types (HPV 16 and 18) that cause approximately 70% of all cases of cervical cancer and two additional HPV types (HPV 6 and 11) that cause 90% of genital warts. Gardasil is the first vaccine approved to prevent cervical cancer. NCI scientists made technological advances that enabled development of Gardasil and subsequent HPV vaccines.

2009: Cervarix

FDA approves Cervarix, a second vaccine that protects against infection by the two HPV types that cause approximately 70% of all cases of cervical cancer worldwide.

2010: The First Human Cancer Treatment Vaccine

FDA approves sipuleucel-T, a cancer treatment vaccine that is made using a patient’s own immune system cells (dendritic cells), for the treatment of metastatic prostate cancer that no longer responds to hormonal therapy. It is the first (and so far only) human cancer treatment vaccine to be approved.

2010: NCI-Sponsored Lung Cancer Screening Trial (NLST)

Initial results of the NCI-sponsored Lung Cancer Screening Trial (NLST) show that screening with low-dose helical computerized tomography (CT) reduced lung cancer deaths by about 20% in a large group of current and former heavy smokers.

2011: Ipilimumab

FDA approves the use of ipilimumab, a monoclonal antibody, for the treatment of inoperable or metastatic melanoma. Ipilimumab stimulates the immune system to attack cancer cells by removing a “brake” that normally controls the intensity of immune responses.

2012: NCI-Sponsored PLCO Cancer Screening Trial

Results of the NCI-sponsored PLCO Cancer Screening Trial confirm that screening people 55 years of age and older for colorectal cancer using flexible sigmoidoscopy reduces colorectal cancer incidence and mortality. In the PLCO trial, screened individuals had a 21% lower risk of developing colorectal cancer and a 26% lower risk of dying from the disease than the control subjects.

2013: Ado-Trastuzumab Emtansine (T-DM1)

FDA approves ado-trastuzumab emtansine (T-DM1) for the treatment of patients with HER2-positive breast cancer who were previously treated with trastuzumab and/or a taxane drug. T-DM1 is an immunotoxin (an antibody-drug conjugate) that is made by chemically linking the monoclonal antibody trastuzumab to the cytotoxic agent mertansine, which inhibits cell proliferation by blocking the formation of microtubules.

2014: Analyzing DNA in Cancer

Researchers from The Cancer Genome Atlas (TCGA) project, a joint effort by NCI and the National Human Genome Research Institute to analyze the DNA and other molecular changes in more than 30 types of human cancer, find that gastric (stomach) cancer is actually four different diseases, not just one, based on differing tumor characteristics. This finding from TCGA and other related projects may potentially lead to a new classification system for cancer, in which cancers are classified by their molecular abnormalities as well as their organ or tissue site of origin.

2014: Pembrolizumab

FDA approves pembrolizumab for the treatment of advanced melanoma. This monoclonal antibody blocks the activity of a protein called PD1 on immune cells, which increases the strength of immune responses against cancer.

2014: Gardasil 9

FDA approves Gardasil 9, a vaccine that protects against infection with the same four HPV types as Gardasil plus five more cancer-causing HPV types that together account for nearly 90% of cervical cancers. It is now the only HPV vaccine available in the United States.

2015: NCI-MATCH Clinical Trial

NCI and the ECOG-ACRIN Cancer Research Group launch the NCI-MATCH (Molecular Analysis for Therapy Choice) clinical trial to test more than 20 drugs and drug combinations based on molecular analysis of tumors in people with cancer. The study is designed to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type.

2015: Talimogene Laherparepvec

FDA approves talimogene laherparepvec (T-VEC) for the treatment of some patients with metastatic melanoma that cannot be surgically removed. T-VEC, the first oncolytic virus approved for clinical use, works by infecting and killing tumor cells and stimulating an immune response against cancer cells throughout the body.

2016: Cancer Moonshot℠

Congress passes the 21st Century Cures Act, which provides funding for the Cancer Moonshot, a broad program to accelerate cancer research by investing in specific research initiatives that have the potential to transform cancer care, detection, and prevention.

2017: Pediatric MATCH

NCI and the Children’s Oncology Group launch Pediatric MATCH, an effort to extend molecular analysis and targeted treatment to children and adolescents with cancer. Like NCI-MATCH, Pediatric MATCH seeks to determine if treating tumors with molecularly targeted drugs based on the tumor’s genetic characteristics rather than the type of cancer or cancer site will be effective.

2017: CAR T-Cell Therapies

FDA approves tisagenlecleucel to treat a form of acute lymphoblastic leukemia in certain children and young adults. FDA subsequently approves axicabtagene ciloleucel for patients with large B-cell lymphomas whose cancer has progressed after receiving at least two prior treatment regimens. Both treatments are chimeric antigen receptor (CAR) T-cell therapies that are personalized for each patient. To create these therapies, T cells are removed from the patient, genetically altered to recognize cancer-specific antigens, grown to large numbers in the lab, and then infused back into the patient to stimulate their immune system to attack cancer cells.

2017: Tumor-Agnostic Approval for Pembrolizumab

FDA extends approval of pembrolizumab to treat metastatic and inoperable solid tumors that have certain genetic changes, wherever they occur in the body, that have progressed following prior treatment and that have no alternative treatment options. With this tissue-agnostic approval, pembrolizumab becomes the first cancer treatment based solely on the presence of a genetic feature in a tumor, rather than a person’s cancer type.

2017: Genomic Profiling Tests

FDA clears two products to test tumors for genetic changes that may make the tumors susceptible to treatment with FDA-approved molecularly targeted drugs. In November, FDA authorizes the MSK-IMPACT test developed and used by Memorial Sloan Kettering Cancer Center to analyze tumors for potentially actionable changes in 468 cancer-related genes. In December, FDA approves the FoundationOne CDx test, which evaluates genetic changes in 324 genes known to fuel cancer growth. The FoundationOne test serves as a companion diagnostic for several FDA-approved drugs targeting five common types of cancer.

2018: TCGA PanCancer Atlas

NIH-funded researchers with TCGA complete an in-depth genomic analysis of 33 cancer types. The PanCancer Atlas provides a detailed genomic analysis of molecular and clinical data from more than 10,000 tumors that gives cancer researchers an unprecedented understanding of how, where, and why tumors arise in humans.

2018: NCI-Sponsored TAILORx Clinical Trial

Results from the NCI-sponsored Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, clinical trial show that most women with early-stage breast cancer do not benefit from having chemotherapy after surgery. The trial used a molecular test that assesses the expression of 21 genes associated with breast cancer recurrence to assign women with early-stage, hormone receptor–positive, HER2-negative breast cancer that hasn’t spread to the lymph nodes to the most appropriate and effective post-operative treatment. It is one of the first trials to examine a way to personalize cancer treatment

2018: Larotrectinib

FDA approves larotrectinib, the first drug that targets tumors with NTRK gene fusions. The approval is for pediatric or adult patients with metastatic or inoperable solid tumors that have worsened after previous treatment anywhere in the body driven by an NTRK gene fusion without a known acquired resistance mutation. Larotrectinib is the second drug approved to treat cancer with specific molecular features regardless of where the cancer is located.

2020: International Pan-Cancer Analysis of Whole Genomes

A consortium of international researchers analyzes more than 2,600 whole genomes from 38 types of cancer and matching normal tissues to identify common patterns of molecular changes. The Pan-Cancer Analysis of Whole Genomes study, which used data collected by the International Cancer Genome Consortium and TCGA, uncovers the complex role that changes throughout the genome play in cancer development, growth, and spread. The study also extends genomic analyses of cancer beyond the protein-coding regions to the complete genetic composition of cells.

Milestones in Cancer Research and Discovery was originally published by the National Cancer Institute and updated August 31, 2020.

Clinical Trials: 5 Things You Should Know

Clinical trials are how progress is made in medicine. “They’re really essential to drive our ability to deliver better cancer care,” says Funda Meric-Bernstam, M.D.

Enrollment in a clinical trial is entirely voluntary, but cancer patients can benefit from joining one while also helping future patients. The insights we gain from clinical trials today helps us improve treatment options that will benefit other patients.

Clinical trials are complex, though, and there are a lot of misconceptions surrounding them. Here’s what you should know before you join a clinical trial – or decide it’s not for you.

Clinical trials are safe

“Safety is the most important thing,” says Ecaterina Ileana Dumbrava, M.D. Because patients on clinical trials are the first ones to receive experimental medications, there are many safeguards in place to ensure they’re not harmed.

In addition to the routine assessments cancer patients receive for standard treatment, clinical trial participants typically need additional clinical visits, lab work, imaging scans and biopsies.

Also, you’re not just communicating with your oncologist and your cancer care team. Patients on clinical trials also have continuous contact with a research team to ensure they’re doing well on the new drug.

“We’re talking to patients, often weekly, to see if they’re experiencing any side effects and just checking in to see if they have any questions,” Meric-Bernstam says. Your clinical trial team also provides guidance on next steps if the patient does experience any side effects. “There’s a lot of help built in with clinical trials to make sure that patients are getting optimal care,” Meric-Bernstam adds.

But the focus on safety doesn’t start there – it happens well before patients are enrolled. “The FDA doesn’t come in just at the end of the trial to approve a drug; they approve the drug before it can be even be administered to patients in the trial,” Dumbrava says.

At MD Anderson, clinical trials are designed by experts and go through several rounds of approval to ensure they’re safe for patients. A proposed clinical trial receives its final approval from the Institutional Review Board (IRB), a committee made up of physicians, nurses, researchers, patients and lawyers.

Clinical trials occur in phases

There are four phases of clinical trials, and each has its own goal. When a new drug or a new drug combination is developed, it’s tested in Phase I clinical trials. These usually have a small number of patients, about 15 to 50. “These trials are designed to determine the safety of the drug or drug combination, and what dose to use in following trials,” Meric-Bernstam says. “We’re also looking efficacy, and identifying which patients are the most likely to benefit from the drug, and, therefore, be enrolled in future studies.”

Phase II clinical trials may focus on a specific cancer type and examine how it responds to the experimental drug or procedure. These trials may enroll patients with specific diseases or based on certain test results called biomarkers.

Phase III clinical trials test whether a new treatment is better than what’s being used as the standard treatment. At this point, the drug or procedure may go to the FDA for approval, but studies of the drug aren’t done. A fourth phase (Phase IV) reviews the new treatment’s long-term benefits and side effects.

Clinical trials don’t just examine new drugs

Although many clinical trials study new medicines, they help improve all aspects of cancer care. They can study new ways of dispensing treatment, explore a new dosage, test a new drug combination or examine a drug’s success in treating different cancer types.

They also focus on ways to prevent cancer or a recurrence as well as ways to reduce treatment side effects. “We want to save more lives, but we also want to maintain patients’ quality of life,” Dumbrava says.

Clinical trials don’t limit your access to other care

“No matter what the scenario, often the best treatment choice is a clinical trial,” Meric-Bernstam says. She notes that if there’s already an effective treatment approach, clinical trials offer the opportunity to build on that to make it more effective. They usually require patients to receive known effective treatment options before starting something that’s more investigational. If there aren’t clear, effective treatments, clinical trials offer access to something new that may work.

“Unfortunately, we don’t know if an experimental treatment will be effective, but that’s true for some standard treatments, too,” Meric-Bernstam says.

If your disease isn’t controlled on a clinical trial, your doctor will stop your participation and may offer another treatment option. In some cases, you may enroll in another clinical trial.

“By joining a trial, you’ll usually be getting a treatment that we think may be better than our current options,” Meric-Bernstam says.

Dumbrava agrees, adding, “At minimum, you’ll be receiving the best treatment available.”

And even if you personally don’t see clinical benefit from the experimental treatment, your participation still helps advance cancer research.

Clinical trials are for patients at all stages of cancer

Although all clinical trials have criteria for the participants, clinical trials are available to patients at all stages of cancer. The eligibility criteria, which is meant to ensure patients’ safety, may include the patient’s age, gender, cancer type and stage, previous treatments and overall health.

Your doctor is the best resource for knowing your treatment options. But don’t hesitate to ask if there are clinical trials that are available to you.

“It’s also an opportunity to pay it forward and truly contribute to better outcomes for future patients,” Meric-Bernstram says.


Research on Causes of Cancer

Why Research on Causes of Cancer Is Critical to Progress against the Disease

Cancer can be caused by many things, including exposure to cancer-causing substances, certain behaviors, age, and inherited genetic mutations.

Studying the causes of cancer helps researchers understand the process of carcinogenesis and identify genetic, environmental, and behavioral risk factors for cancer. This knowledge can lead to new ways of preventing and treating the disease.

Research on the causes of cancer also creates opportunities to improve public health, not only by identifying cancer risk factors in populations, but also by providing data that regulatory agencies can use to set safety standards or reduce exposure to toxins that are found to be associated with cancer. Findings from this area of research can also inform the development of advances such as safer computed tomography (CT) scans and risk-reducing surgeries.

Researchers use many different approaches to identify potential causes of cancer, from cell-based and animal studies to human observational studies. Research in basic cancer biology can reveal the mechanisms by which biological, chemical, and physical carcinogens initiate and promote cancer. Genetic analyses, such as genome-wide association studies, exome sequencing, and whole-genome sequencing, allow researchers to identify genetic changes that may be associated with cancer risk. Epidemiological approaches—including cohort studiescase-control studies, exposure-assessment studies, family studies, and genomic studies—are used to identify possible causes of cancer and study the patterns of risk in large populations.

Another approach, known as descriptive epidemiology, characterizes trends in cancer incidence and mortality within a given population, between populations over time, and in relation to overall patterns of exposure in populations to yield clues that may point researchers to cancer causes and risk factors. This type of research can also identify emerging trends in cancer incidence.

Opportunities in Research on Causes of Cancer

Advances in technology are improving how we determine and measure risk factors, enabling researchers to store and access findings in online databases, and allowing teams of investigators worldwide to pool data on an unprecedented scale. Multidisciplinary research teams are increasingly common and often include a range of experts, including epidemiologists, physicians, computational biologists, statisticians, oncologists, toxicologists, and geneticists.

Technological advances have also led to more accurate studies of substances in the environment suspected of causing cancer. Developing devices that can accurately measure environmental exposures and biochemical assays in biologic specimens that might be associated with cancer could improve researchers’ ability to identify cancer-causing agents.

Identifying people at highest risk of cancer, such as those with an inherited susceptibility to cancer or those who have been exposed to carcinogens, creates opportunities to develop risk prediction models and allows health providers to focus prevention and screening interventions on those most likely to benefit.

Challenges in Research on Causes of Cancer

Demonstrating cause-and-effect relationships in population studies examining potential cancer risk factors is a challenge because there are often many possible explanations for observed associations between a risk factor and cancer. Rare cancers and uncommon exposures, in particular, present challenges for researchers studying the causes of cancer. New statistical methods may be needed to improve the analysis of datasets of all sizes from these studies.

When studying certain exposures, such as dietary exposures, identifying which component is associated with an increased or decreased risk of cancer can also be a challenge. Retrospective studies have additional limitations, such as participants’ inability to accurately remember and report past exposures or exposure levels.

There is a continual need for new and improved techniques for measuring risk factors and exposures to potential causes of cancer. For example, studies that estimate radiation exposures among an exposed population must also quantify the uncertainties inherent to those estimates.

To identify cancer causes and risk factors that may be experienced by only a portion of the population, very large studies may be needed to have the statistical power required to establish an association.

Investigating interactions between genes and environmental exposures that have been associated with cancer is a challenge because some of these studies involve enormous data sets and require sophisticated computational analyses. Once a causative agent has been identified, another challenge is figuring out how to reduce a person’s exposure or ameliorate its harmful effects.

Although genome-wide association studies can point to chromosomal regions associated with cancer risk in certain populations, additional studies and analyses are needed to identify the specific genetic changes involved and to understand how they play a role in the development of cancer.

NCI’s Role in Research on Causes of Cancer

NCI funds extramural research on the causes of cancer and conducts intramural research in this area. The intramural research program allows the institute to conduct studies that require long-term, sustained support and provides NCI with the flexibility to redirect resources, when necessary, to respond quickly to emerging public health concerns.

NCI and NCI-funded researchers aim to understand the exposures and risk factors that cause cancer, as well as the genetic basis for cancer development.

Studies conducted by the NCI Cohort Consortium, for example, seek to identify factors (including environmental, lifestyle, and genetic) that may influence cancer risk. The consortium is a partnership between intramural and extramural investigators that pools the large quantity of data and biospecimens necessary to conduct a wide range of cancer studies. The consortium consists of investigators responsible for more than 50 cohorts that include more than 7 million people in the United States and around the globe.

Intramural and extramural investigators also seek to identify ways to translate these research findings into tangible benefits to prevent cancer, identify and monitor those at risk, and develop clinical and public health interventions.

Environmental and Behavioral Risk Factors

NCI’s Division of Cancer Epidemiology and Genetics (DCEG) and the Epidemiology and Genomics Research Program in NCI’s Division of Cancer Control and Population Sciences (DCCPS) conduct and fund research to identify and evaluate a range of exposures and risk factors that may be associated with cancer, including:

DCEG researchers and those funded by DCCPS are also studying risks of second primary cancers. Nearly one in five cancers occurs in an individual with a previous diagnosis of cancer, and these second cancers are a leading cause of morbidity and mortality among cancer survivors. Research on treatment, lifestyle, environmental, and medical history factors associated with second cancers is ongoing, as is research on genetic susceptibility to second cancers.

Genetic Factors

NCI and NCI-funded investigators are also studying genetic factors that may predispose individuals to cancer and gene–environment interactions in cancer risk using approaches such as genome-wide association studies and whole genome scans.

Changes in an individual’s genes, including gene mutations, genetic modifiers, and polymorphisms, can alter his or her lifetime risk of cancer. To explain the genetic factors that influence a person’s risk for cancer, NCI and NCI-funded investigators are:

  • conducting human genetic studies to identify and validate key susceptibility genes and their modifiers using knowledge gained from gene expression profiles and protein “fingerprints”
  • identifying genetic and environmental factors that influence the cancer epigenome (i.e., chemical modifications to DNA that do not involve DNA sequence changes)
  • defining the role of inherited or acquired genetic alterations, in combination with lifestyle factors and environmental exposures (such as radiation and chemicals), as important determinants of an individual’s cancer susceptibility
  • identifying new tumor suppressor genes and oncogenes, and elucidating their mechanisms of action
  • identifying, mapping, and characterizing genes and chromosome regions that are involved in tumor initiation and progression

For example, investigators in DCEG’s Radiation Epidemiology Branch are partnering with investigators from the Childhood Cancer Survivor StudyExit Disclaimer to conduct a genome-wide association study of second cancers in childhood cancer survivors.

NCI researchers are also studying a range of hereditary cancer syndromes that predispose affected individuals and their family members to cancer. These include inherited bone marrow failure syndromesLi-Fraumeni syndromeDICER1 syndrome, familial melanoma, and others. Studies of people with hereditary cancer syndromes help researchers understand the underlying biology of cancer risk and develop ways to improve the management of these disorders.

Such studies may also, indirectly, provide insights into the genetic basis for noninherited, or sporadic, forms of cancers. That was the case with research on familial kidney cancer by W. Marston Linehan, M.D., of NCI’s Center for Cancer Research (CCR).

How Exposures and Risk Factors Act

NCI supports and conducts research to understand the mechanisms by which external exposures and risk factors induce and promote cancer.

NCI’s Division of Cancer Biology (DCB) supports research investigating the role of biological agents and host factors that contribute to cancer. DCB’s Cancer Immunology, Hematology and Etiology Branch, for example, funds research on the role of the microbiome in cancer development and the influence of aging on cancer susceptibility. DCB also supports research to understand mechanisms by which carcinogens initiate and promote tumor development.

CCR researchers are trying to elucidate mechanisms that influence tumor initiation, promotion, and progression, including those associated with lifestyle, the environment, inflammation, the immune system, viruses, and host-tumor interaction.

NCI’s Office of HIV and AIDS Malignancy (OHAM) coordinates and oversees NCI research programs that focus specifically on HIV/AIDS and AIDS-associated cancers. For example, OHAM’s AIDS and Cancer Specimen Resource is a biorepository for HIV-infected human biospecimens that serves as a resource for investigators conducting basic research in the pathogenesis of AIDS-related malignancies.


Research on Causes of Cancer was originally published by the National Cancer Institute.

The Importance of Cancer Treatment Research

Research on the treatment of cancer is fundamental to improving outcomes for all patients affected by the disease. Despite the tremendous progress made in recent decades in treating many types of cancer, effective therapies are still lacking for some forms of the disease, including liver cancer, pancreatic cancer, and certain types of adult and pediatric brain cancer. More than 600,000 people are projected to die from cancer in the United States in 2020.Also, too many patients whose cancer has been successfully treated experience long-term adverse effects of the disease and its treatment, including increased risk of a second cancer. Therefore, cancer treatment research includes developing ways to prevent or lessen the side effects of treatment. More research is needed to ensure that all patients with cancer have safe and effective therapies and the highest possible quality of life.

Thanks to NCI-funded research, patients with cancer have a greater number of more-effective and less-toxic therapeutic options than ever before. NCI has played a vital role in cancer drug discovery and development for more than 50 years. NCI’s support for cancer treatment research extends from studies of the fundamental biology of cancer, the development of treatments that target cancer cell abnormalities, and the testing of new cancer therapies in clinical trials.

NCI’s contributions are reflected in the fact that:

  • Approximately half of the drugs currently used to treat patients with cancer were discovered and/or developed by NCI-supported researchers. These include imatinib (Gleevec), the first small-molecule molecularly targeted therapy; ipilimumab (Yervoy), the first immune checkpoint inhibitor; and tisagenlecleucel (Kymriah), the first genetically engineered cell-based immunotherapy.
  • In 2019 alone, 11 new cancer treatments were approved by the Food and Drug Administration, and NCI-funding contributed to the development and/or testing of most of them.
  • study published in 2019 showed that nearly half of the phase 3 clinical trials conducted by the SWOG Cancer Research Network, one of five National Clinical Trials Network clinical research groups, were associated with changes in cancer clinical practice guidelines or new drug approvals.

The Future of Cancer Treatment Research

Breakthroughs in molecularly targeted therapies and immunotherapy have revolutionized the cancer treatment landscape for patients. Additional cancer treatment innovations are on the horizon. For example, recent research is creating optimism that, one day, there may be targeted treatments for so-called “undruggable” cancer targets, including the oncoproteins RAS and MYC, and for restoring the tumor-suppressor function of proteins such as p53 and PTEN. Although more development and clinical testing are needed, the availability of these targeted treatments will be a hallmark of unprecedented progress for patients who have few therapeutic options.

Many other important research opportunities exist to improve the care and treatment of the individual patient. One day, not only will it be possible to molecularly characterize a patient’s cancer cells, but the cellular components of their tumor—and even the composition of their intestinal or tumor microbiome—will inform treatment decisions. With this information, doctors will select therapies, or combinations of therapies, for each patient and avoid ones that will have unacceptable side effects. This future will only be possible through additional research investment.


All patients with cancer will have safe and effective treatments.


Additional investments in cancer treatment research will further improve the outlook for both adults and children with cancer. Fully realizing the potential to identify, study, and test new cancer therapies requires additional research to achieve the following goals:

1) Discover and develop new cancer therapies, including those that involve molecularly targeted therapies and immunotherapies, as well as treatment combinations

Treatments that target the molecular changes in a person’s cancer and immunotherapies that unleash the power of the immune system against the disease are revolutionizing the potential of cancer care. Because these newer therapies provide durable clinical benefits to only a small proportion of patients, new or revised therapeutic approaches must be developed. Among our major objectives of this research are:

  • Identifying and characterizing new targets for cancer treatment, such as abnormal proteins that are responsible for cancer cell survival, growth, and spread
  • Developing new ways to leverage the rapid progress in cancer immunotherapy to benefit more patients, including identifying predictive biomarkers of efficacy or toxicity, developing novel immune targets, and combining therapies
  • Understanding the mechanisms of drug resistance, a major cause of treatment failure in patients, and developing strategies that target these mechanisms, including the use of combination therapies
  • Identifying and developing additional biomarkers to monitor treatment benefits and harms and to aid clinicians in selecting the most appropriate treatments for patients

2) Improve traditional cancer treatment approaches, including surgery, radiation therapy, and chemotherapy

Surgeryradiation therapy, and chemotherapy remain important options for cancer treatment. NCI funds research to improve the effectiveness and use of these treatments. We must learn to use them more precisely and minimize their side effects. NCI’s major objectives include:

  • Understanding how to combine therapies, including different types of treatment (for example, radiotherapy with immunotherapy)
  • Tailoring treatments to avoid overtreatment and avoidable toxic side effects (for example, by conducting de-escalation studies)
  • Advancing the development of precision radiotherapy to target tumors more precisely and spare the surrounding normal tissue from radiation damage
  • Supporting innovations in cancer surgery, including approaches to minimize the impact on normal tissues

Cancer Treatment Research was originally published by the National Cancer Institute.  Updated August 30, 2020.