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100 Years of Advances Against Cancer

100 Years of Advances Against Cancer - 1900s-1930s

100 Years of Advances Against Cancer - 1940s-1950s

100 Years of Advances Against Cancer - 1960s

100 Years of Advances Against Cancer - 1970s

100 Years of Advances Against Cancer - 1980s

100 Years of Advances Against Cancer - 1990s

100 Years of Advances Against Cancer - 2000s

100 Years of Advances Against Cancer

The past 100 years have seen many remarkable advances against cancer, a disease known to mankind for thousands of years. The accomplishments of the last 30 years in particular, such as the development of monoclonal antibodies and other targeted therapies, the identification of cancer-associated genes, the introduction of computer-assisted imaging, and the decline in cancer deaths since the mid-1990s, have all built on knowledge gained in earlier decades.

1900s

1903	Radium is found effective in the treatment of tumors (Marie and Pierre Curie isolated radium in 1898).
1907	The American Association for Cancer Research (AACR) is founded.

1910s

1911	Peyton Rous discovers a virus that causes cancer in chickens (Rous sarcoma virus).
1912	Cancer cells are grown in the laboratory, the first long-term "tissue culture."
1913	The first known article on cancer's warning signs is published in a popular women's magazine (Ladies' Home Journal). A nationwide organization dedicated to public education about cancer is formed (the American Society for the Control of Cancer, which later became the American Cancer Society).
1915	Coal tar gives rabbits cancer in experimental proof of carcinogenesis. The theory that chemicals had cancer-causing potential began with observations more than a century earlier on the high rate of cancer among chimney sweeps.

1920s

1922	The Public Health Service opens a Special Cancer Investigations Laboratory at Harvard Medical School.
1928	George Papanicolaou finds vaginal cell smears (the Pap smear) can reveal the presence of cervical cancer.

1930s

1930	The National Institute of Health is established by the Ransdell Act.
1937	Legislation signed by President Franklin D. Roosevelt establishes the National Cancer Institute to support research related to the causes, diagnosis, and treatment of cancer.

1940s

1940	The first issue of the Journal of the National Cancer Institute is published.
1941	Charles Huggins discovers that blocking male hormones (by removal of the testicles or administration of estrogens) could cause the regression of prostate tumors. The "hormonal therapy" of prostate cancer is still used today.
1943	The Pap smear is introduced into medical practice.
1944	DNA is found by Oswald T. Avery, Colin MacLeod, and Maclyn McCarty to be the basic genetic material.
1947	Sidney Farber finds that a folic acid derivative inhibits acute leukemia. This first antimetabolite leads to a category of drugs that interfere with cell processes because they share structural similarities with compounds required in normal cell activities.
1948	George Hitchings synthesizes 6-mercaptopurine (6-MP), an antimetabolite, to combat childhood leukemia.
1949	The Food and Drug Administration (FDA) approves nitrogen mustard (mechlorethamine), a drug that interacts with DNA chemically (an alkylating agent) to kill cancer cells.

1950s

1950	Ernst Wynder, Evarts Graham, and Sir Richard Doll confirm the cigarette smoking-cancer link.
1952	DNA is found to be the genetic material of some viruses.
1953	James Watson and Francis Crick discover the structure of DNA. The FDA approves methotrexate, an antimetabolite derived from folic acid, and 6-mercaptopurine as anticancer drugs.
1955	NCI's Clinical Trials Cooperative Group Program is established. The National Chemotherapy Program begins. Roy Hertz and Min Chiu Li achieve total cure of a human solid tumor, choriocarcinoma.
1957	Alick Isaacs and Jean Lindenmann discover interferon, a virus fighter made by cells. Charles Heidelberger introduces 5-fluorouracil (5-FU), a new type of anticancer drug that resulted from rational design.
1958	NCI scientists pioneer the use of combination chemotherapy. Partial and complete remissions, as well as prolonged survival, were observed in children and adults with acute leukemia who were treated with combinations of 6-mecaptopurine and methotrexate.
1959	Cyclophosphamide (Cytoxan), an alkylating agent designed to improve the selectivity of cancer drugs, is approved by the FDA.

1960s

1960	Chromosome abnormalities are associated with leukemias.
1961	Marshal Nirenberg and others prove the triplet code is how the information to make proteins is stored in DNA. The Food and Drug Administration (FDA) approves vinblastine, a drug that binds to tubulin, the protein building block of fiber-like structures called microtubules that play a key role in cell division. The drug is derived from the ornamental shrub, Vinca rosea.
1962	The Royal College of Physicians issues a report on smoking and health. The FDA approves 5-FU as an anticancer drug.
1963	The FDA approves vincristine, a sister drug to vinblastine. The Health Insurance Plan (HIP) of Greater New York Study begins. HIP is the first randomized controlled trial of periodic breast cancer screening with mammography.
1964	The U.S. Surgeon General issues a report on reducing the health consequences of smoking. A virus (the Epstein-Barr virus) is linked to human cancer (Burkitt lymphoma) for the first time. The American Society of Clinical Oncology (ASCO) is established. The anticancer drug melphalan (L-PAM) is approved by the FDA.
1966	NCI standardizes the testing of cancer-causing chemicals.
1967	The guaiac fecal occult blood test (FOBT) is introduced as a screening test for colorectal cancer. Guaiac is found in the wood of the tree Guaiacum officinale and can be used to detect hemoglobin in stool samples.
1969	Robert Heubner and George Todaro propose the oncogene hypothesis. An oncogene is a gene that has the potential to make a cell become cancerous. Oncogenes arise from normal genes, or proto-oncogenes, by mutation or by increased expression.

1970s

The importance of proto-oncogenes in normal cellular growth control is established.

The cytochrome P450 enzyme system is shown to activate many carcinogens.

Flexible sigmoidoscopy and colonoscopy are introduced to help find and remove precancerous growths in the colon. Clinical studies conducted over the next 30 years establish that sigmoidoscopy can help reduce both colon cancer incidence and mortality.

Positron emission tomography (PET) is developed.

Limb-sparing surgeries are developed for sarcomas of the extremities (late 1970s). Statistical methods are developed to control simultaneously for several factors in the analysis of studies and to quantify cancer risks (1970s and 1980s).

Studies in human populations link cancer risk to infectious agents, such as human papillomavirus (HPV) for cervical cancer and hepatitis B virus (HBV) for liver cancer (1970s and 1980s).

Studies clarify the patterns of cancer risk following exposure to ionizing radiation (1970s and 1980s).

Studies link cancer risks to hormonal drugs, such as diethylstilbestrol (DES) taken during pregnancy and hormonal replacement therapy (1970s and 1980s).

Statistical methods for genetics are developed to define modes of inheritance, localize genes, and evaluate gene-environment interactions in cancer risk (1970s through 1990s).

Precursor lesions are linked to several forms of cancer, for example, "dysplastic nevi" to melanoma (late 1970s and early 1980s).

1970	Howard Temin and David Baltimore discover the enzyme reverse transcriptase. Reverse transcriptase and bacterial restriction enzymes are keys to gene cloning and engineering. Recombinant DNA techniques are developed for cloning genes in the mid-1970s.
1971	President Richard M. Nixon converts the Army's former biological warfare facilities at Ft. Detrick, Maryland, to house research activities on the causes, treatment, and prevention of cancer. The prevalence of U.S. adult smoking is 37 percent. Cisplatin, a platinum-containing anticancer compound with unique biologic effects, enters clinical trials. President Nixon signs the National Cancer Act of 1971 on December 23.
1973	The Surveillance, Epidemiology, and End Results (SEER) Program is established. Computed tomography (CT) is introduced in the United States. Certification in medical oncology and gynecologic oncology is first offered.
1974	The Food and Drug Administration (FDA) approves doxorubicin (Adriamycin), an antitumor anthracycline antibiotic from Streptomyces bacteria. CANCERLINE, a national database of published cancer research, is established.
1975	Hybridoma technology is developed for the production of monoclonal antibodies. Southern blot technique is developed to analyze DNA fragments. DNA sequencing methods are developed. The Society for Surgical Oncology and Oncology Nursing Society are established.
1976	The first of some 50 now known human proto-oncogenes is discovered (src). Interleukin-2 is discovered. NCI's Cancer Information Service (1-800-4-CANCER) begins operation.
1977	The first national cancer patient education program (I Can Cope) is founded. NCI establishes the first electronic registry of cancer clinical trials (CLINPROT). This registry is the first cancer information product included in what would later become known as the Physician Data Query (PDQ) database.
1978	The first human testing of a biological therapy is conducted (alpha-interferon). Tamoxifen, an anti-estrogen drug, is approved by the FDA for the treatment of breast cancer. Metastatic cells are shown to arise from pre-existing subpopulations of cells in primary tumors. The FDA approves cisplatin (Platinol) for use in combination with other drugs in the treatment of metastatic testicular and metastatic ovarian cancer.
1979	The most frequently mutated gene in human cancer, p53, is discovered. The p53 gene is a tumor suppressor gene. Tumor suppressor genes are genes whose protein products control normal cell growth. Modified radical mastectomy replaces radical mastectomy for breast cancer.

1980s

The first highly effective anti-nausea drugs are developed to alleviate this side effect of chemotherapy.

Continuous pain medication infusion pumps are developed.

Biochemical and genetic assays are integrated into epidemiologic studies (molecular epidemiology).

Magnetic resonance imaging (MRI) is introduced in the early 1980s.

Severe combined immunodeficiency (SCID) mice are developed in the mid-1980s. These mice play an important role in cancer research.

1980	NCI scientists isolate human T-cell lymphotrophic virus 1 (HTLV-1). This virus, which is also called adult T-cell leukemia virus, is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and several other diseases.
1981	The first human viral vaccine that can prevent cancer (hepatitis B virus vaccine for liver cancer) is introduced.
1982	The first major DNA sequence databases are established in the United States (GenBank) and Germany. NCI's Physician Data Query (PDQ) cancer information database goes online. PDQ is made available through a dial-up connection to the U.S. National Library of Medicine.
1983	The restriction fragment length polymorphism (RFLP) technique, which is a DNA analysis technique, is used in cancer research. Computerized tomography of the colon (virtual colonoscopy) is proposed as a screening method to identify colon polyps and colorectal cancer.
1984	Dietary guidelines to reduce cancer are introduced. The human p53 gene is cloned.
1985	Lumpectomy plus radiation therapy is found equivalent to mastectomy for early breast cancer. The polymerase chain reaction technique (PCR) is introduced. This technique allows millions of copies of an individual segment of DNA to be made from a single copy. Nerve-sparing prostatectomy, designed to preserve potency and urinary continence, is introduced.
1986	The human HER2 proto-oncogene is cloned. HER2 is also called neu and erbB2.
1987	The human retinoblastoma (Rb) gene is cloned. Rb is a tumor-suppressor gene associated with the pediatric eye cancer retinoblastoma.
1988	Post-operative (adjuvant) chemotherapy is proven to increase disease-free survival in women with early breast cancer. The Bethesda System Conference develops a system for standardized reporting of Pap smear results.
1989	Adjuvant chemotherapy is proven to increase survival in colon cancer. The Human Gene Mapping database is established. Carboplatin, a drug related to cisplatin, is approved by the Food and Drug Administration. Certification in radiation oncology is first offered.

1990s

After increasing steadily for decades, overall cancer death rates in the United States stabilized in the early 1990s and began to decrease in 1994, a trend that continues today.

The transition from film-based radiology to digital computer-assisted medical imaging begins.

The multi-step nature of carcinogenesis is proven. That is, more than one gene mutation is required for a cell to become cancerous.

The fluorescence in situ hybridization (FISH) technique, allowing researchers to study gene copy number and chromosomal location inside cells, is developed.

Several common genetic variants are linked to the risk of lung and other cancers.

1990	Results from the first chemoprevention trial to show efficacy (vitamin A analogue against mouth and throat tumors) are reported.
1991	The first human gene therapy for cancer (melanoma) is attempted. Post-operative (adjuvant) radiation therapy and chemotherapy are found to improve survival in rectal cancer. Two white blood cell colony-stimulating factors (G-CSF and GM-CSF) are approved by the Food and Drug Administration (FDA) to treat the neutropenia caused by cancer therapy.
1992	The Mammography Quality Standards Act is passed. Paclitaxel (Taxol) is approved by the FDA. Found in the bark of the Pacific yew tree, Taxus brevifolia, this drug acts to stabilize fiber-like structures called microtubules that play a key role in the cell division cycle.
1993	The first gene associated with hereditary nonpolyposis colon cancer (HNPCC) is cloned (hMSH2). People with HNPCC are at increased risk of developing colon cancer.
1994	BRCA1 is the first breast cancer-associated gene cloned. The Alpha-Tocopherol Beta-Carotene (ATBC) Cancer Prevention Study finds no benefit from the use of beta-carotene supplements in smokers and a possible increased risk of lung cancer. Human herpesvirus 8 (HHV-8), a causative agent for Kaposi's sarcoma, is identified. HHV-8, also known as Kaposi's sarcoma-associated herpesvirus, is later linked to primary effusion lymphoma and multicentric Castleman disease.
1995	The BRCA2 gene is cloned. The FDA approves tretinoin, a differentiating agent related to vitamin A, for use in the treatment of acute promyelocytic leukemia. Tretinoin is also known as all-trans retinoic acid (ATRA). Porfimer sodium, a light-sensitive drug that can be absorbed by tumors, is approved by the FDA, permitting photodynamic therapy of some types of cancer. Information in NCI's Physician Data Query (PDQ) database becomes available on the World Wide Web via the NCI Web site CancerNet.
1996	Topotecan (Hycamptin), the first of a class of drugs that interferes with the enzyme topoisomerase I, is approved by the FDA for the treatment of metastatic ovarian cancer. Topoisomerases uncoil DNA during DNA replication, and altering the work of this enzyme leads to tumor cell death. Topotecan is derived from the bark of a Chinese tree known as Camptotheca acuminata. The FDA approves another topoisomerase 1 inhibitor - irinotecan (Camptosar) - for the treatment of metastatic colorectal cancer. Two major studies of beta carotene supplements (The Physicians' Health Study and the Beta-Carotene Retinol Efficacy Trial) show no cancer prevention benefit.
1997	The Cancer Genome Anatomy Project (CGAP), a multi-year project to assemble the first index of genes involved in cancer, is launched. The first biotechnology product approved by the FDA to treat patients with cancer - a monoclonal antibody called rituximab (Rituxan) - is used to treat non-Hodgkin lymphoma (NHL). NCI and Chinese scientists find that occupational exposure to benzene is associated with increased risks of developing acute non-lymphocytic leukemia and related myelodysplastic syndromes and NHL. The National Cancer Advisory Board recommends that NCI should advise all women age 40 years and older to receive screening mammograms every one to two years. Cancer stem cells are first identified in acute myelogenous leukemia. They will later be identified in additional cancer types, including cancers that form solid tumors. Cancer stem cells are rare cells that have the ability to proliferate extensively and initiate cancer when injected into animals. Cancer stem cells in solid tumors are the only tumor cells that have the ability to initiate new tumors.
1998	Results from the Breast Cancer Prevention Trial show that the incidence of breast cancer among women who are at increased risk of the disease can be reduced by 50 percent with the drug tamoxifen. The FDA subsequently approves tamoxifen for the prevention of breast cancer. Trastuzumab (Herceptin), a monoclonal antibody that targets cancer cells that overproduce the protein HER2, is approved by the FDA for the treatment of metastatic breast cancer. HER2 is overproduced in the tumors of approximately 25 percent to 30 percent of women with advanced disease. The prevalence of U.S. adult smoking is 24.1 percent.
1999	The Hybrid Capture II human papillomavirus (HPV) DNA test is approved by the FDA as a test that can be used in conjunction with the Pap smear in screening for cervical cancer.

2000s

2000	Researchers discover that the most common form of non-Hodgkin lymphoma (NHL), diffuse large B-cell lymphoma, is actually two distinct diseases, explaining why only 40 percent of patients with NHL can be cured by chemotherapy. NCI establishes the Center to Reduce Cancer Health Disparities as part of a major national commitment to identify and address the underlying causes of disease and disability in racial and ethnic communities.
2001	The drug imatinib mesylate (Gleevec) is shown to be effective against chronic myelogenous leukemia (CML). Imatinib mesylate is the first anticancer drug developed specifically to target the molecular defect that causes a particular type of cancer.
2002	NCI launches the National Lung Screening Trial (NLST) to determine whether spiral computed tomography is better than single-view chest x-ray in reducing deaths among current and former heavy smokers. The International Agency for Research on Cancer (IARC) publishes a monograph on tobacco smoke and involuntary smoking (second-hand smoke) that classifies second-hand smoke as carcinogenic to humans.
2003	Two randomized controlled trials show that taking aspirin daily for as little as three years reduces the development of colorectal polyps by 19 percent to 35 percent in individuals at high risk for colorectal cancer. Results from the Prostate Cancer Prevention Trial (PCPT) show that men taking finasteride had 25 percent fewer diagnoses of prostate cancer than men taking a placebo, proving that prostate cancer can be prevented. An NCI-supported international clinical trial finds that postmenopausal women diagnosed with early-stage breast cancer who took the drug letrozole, an aromatase inhibitor, after completing an initial five years of adjuvant therapy with tamoxifen had a significantly reduced risk of cancer recurrence compared to women taking a placebo. The Food and Drug Administration (FDA) approves the drug bortezomib (Velcade) for the treatment of multiple myeloma. Bortezomib represents a new class of targeted agents that inhibit proteasomes, structures inside cells that degrade proteins.
2004	Letrozole is approved by the FDA for the adjuvant treatment of early-stage breast cancer after five years of tamoxifen therapy. NCI collaborates with the Department of Health and Human Services to establish a National Network of Tobacco Cessation Quitlines. Palifermin (Kepivance) is approved by the FDA to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies who receive high doses of chemotherapy and radiation therapy followed by stem cell rescue. Data from the Women's Health Initiative (WHI) study show that women who take estrogen in combination with the hormone progestin have a greater risk of developing breast cancer than women who take estrogen alone and that estrogen-alone hormone replacement therapy has no overall benefit in disease prevention, specifically on the risks of breast and colorectal cancer. The monoclonal antibody bevacizumab (Avastin) is approved by the FDA for use with other drugs in the treatment of metastatic colorectal cancer. Bevacizumab targets a protein called vascular endothelial growth factor, which stimulates the growth of new blood vessels to tumors (a process called tumor angiogenesis). The monoclonal antibody cetuximab (Erbitux) is approved by the FDA for the treatment of metastatic colorectal cancer. Cetuximab targets a protein called epidermal growth factor receptor, which is overexpressed in some cancers. The FDA approves oxaliplatin (Eloxatin) for use in the treatment of advanced colorectal cancer. The prevalence of U.S. adult smoking declines to 20.9 percent.
2005	Preliminary results from the Digital vs. Film Mammographic Imaging Screening Trial (DMIST) show no difference in breast cancer detection in the general population of women who participated in the study. However, women with dense breasts who are pre- or perimenopausal or women who are younger than age 50 may benefit from having a digital rather than a film mammogram. Results from two large NCI-sponsored randomized clinical trials show that patients with early-stage, HER2-positive, invasive breast cancer who received the monoclonal antibody trastuzumab (Herceptin) in combination with chemotherapy experienced a significant decrease in their risk of cancer recurrence in comparison with patients who received the same chemotherapy without trastuzumab. NCI and the National Human Genome Research Institute announce the launch of The Cancer Genome Atlas (TCGA) Project, which, in its initial phase, will systematically explore the genomic changes in lung, brain (glioblastoma), and ovarian cancer. The FDA approves an albumin-stabilized nanoparticle formulation of paclitaxel (Abraxane) for use in the treatment of metastatic or recurrent breast cancer.
2006	Initial results from the Study of Tamoxifen and Raloxifene (STAR) show that the drug raloxifene reduces the incidence of invasive breast cancer to the same extent (approximately 50 percent) as tamoxifen, but it appears less likely to cause some of the potentially dangerous side effects found with tamoxifen. The FDA approves the vaccine Gardasil, which protects against persistent infection by the two types of HPV that cause approximately 70 percent of cervical cancers worldwide. NCI scientists developed the underlying technology used to make this vaccine. The U.S. Surgeon General releases a report on the harmful health consequences of involuntary exposure to tobacco smoke (second-hand smoke). The FDA approves trastuzumab (Herceptin) for use with other drugs in the adjuvant treatment of women with early-stage, node-positive, HER2-overexpressing breast cancer. NCI launches the TAILORx trial to determine whether gene expression patterns in early-stage breast cancer can distinguish between women who are at high risk of cancer recurrence and, therefore, most likely benefit from adjuvant chemotherapy and women who have a low risk of recurrence and, thus, can be spared the toxic side effects of chemotherapy. The prevalence of U.S. adult smoking declines to 20.8 percent.
2007	Results from a large phase III clinical trial show that adult patients with previously untreated acute promyelocytic leukemia who were treated with arsenic trioxide after standard chemotherapy had longer disease remissions and better overall survival than patients who received standard chemotherapy alone.
2008	Results from a large multicenter study show that the accuracy of computerized tomographic colonography (virtual colonoscopy) is similar to that of conventional, optical colonoscopy in detecting intermediate-size and large colorectal polyps, suggesting that the procedure could serve as an initial screening exam for colorectal cancer. In contrast with earlier research suggesting that dietary supplementation with selenium and vitamin E may lower the risk of prostate cancer, initial results from the largest-ever prostate cancer prevention study, the Selenium and Vitamin E Cancer Prevention Trial (SELECT), show that these substances do not help prevent prostate cancer.