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# Milestones in Cancer Research and Discovery

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### Milestones in Cancer Research and Discovery (Text-Only Version)

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 Oncogene Identified**

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.

                        - Posted:  January 21, 2015

at the National Institutes of Health

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