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<languages/>
== 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 inherited 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 one of his wife's hands.

'''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 Ichakawa 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'''

The Food and Drug Administration (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'''

The Food and Drug Administration (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'''

The Food and Drug Administration (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 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%. The Food and Drug Administration (FDA) approves tamoxifen to reduce the incidence of breast cancer in women at increased risk.

'''1998: Trastuzumab'''

The Food and Drug Administration (FDA) approves trastuzumab, a monoclonal antibody that targets cancer cells that overproduce the protein HER2, 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). 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'''

The Food and Drug Administration (FDA) approves the human papilloma virus (HPV) vaccine Gardasil, which protects against infection by the two types of HPV that cause approximately 70% of all cases of cervical cancer. NCI scientists developed the underlying technology used to make Gardasil.

'''2009: Cervarix'''

The Food and Drug Administration (FDA) approves Cervarix, a second vaccine that protects against infection by the two types of the human papilloma virus (HPV) that cause approximately 70% of all cases of cervical cancer worldwide. NCI scientists developed the underlying technology used to make Cervarix.

'''2010: The First Human Cancer Treatment Vaccine'''

The Food and Drug Administration (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 Tiral (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'''

The Food and Drug Administration (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, 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)'''

The 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'''

The 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.

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