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150 Years of Advances Against Cancer

  • Updated: 01/06/2011

Introduction

During the past 150 years, we have witnessed many remarkable advances against cancer, a disease known to humanity for thousands of years. The advances highlighted below represent a sampling of what has been accomplished to date. Although we still have a long way to go to reduce the toll of cancer in the United States and worldwide, our research and public health efforts are beginning to pay dividends. Since the early 1990s, we have witnessed a sustained decline in the rate of cancer deaths in the United States. We must now redouble our efforts to ensure continued progress and, hopefully, to accelerate the pace of our advances.

150 Years of Advances Against Cancer - 1860s-1890s


1860s
1863Rudolph Virchow identifies white blood cells (leucocytes) in cancerous tissue, making the first connection between inflammation and cancer. He hypothesizes that cancer develops at sites of chronic inflammation. Previously, he had proposed that all cells, including cancer cells, arise from the division (multiplication) of pre-existing cells. He also coined the term “leukemia” and was the first person to describe the excess number of white blood cells in the blood of patients with this disease.
1870s
1873Theodore Billroth performs the first successful surgery to treat cancer of the larynx (voice box).
1877Vincenz Czerny performs the first successful surgery for cancer of the esophagus (carcinoma of the cervical, or upper, esophagus). His patient lives 1 year before dying from a recurrence of the tumor.
1878

Wilhelm Freund successfully removes a woman’s uterus (abdominal hysterectomy) to treat uterine cancer.

Richard von Volkman performs the first surgical excision of rectal cancer.

1880s
1881Theodore Billroth performs the first successful surgery to treat gastric (stomach) cancer. His patient lives 4 more months before dying of liver metastases.
1882William Halsted performs the first radical mastectomy to treat breast cancer. In this surgical procedure, the entire breast, the lymph nodes under the arm (axillary lymph nodes), and the chest muscles behind the breast (pectoralis major and pectoralis minor muscles) are removed. Radical mastectomy will remain the standard operation for breast cancer until latter half of the 20th century, when the use of modified radical mastectomy becomes widely accepted.
1890s
1895Wilhelm Roentgen discovers X-rays. The first X-ray picture is an image of one of his wife’s hands.
1898Marie and Pierre Curie discover the radioactive elements radium and polonium. Within a few years, the use of radium in cancer treatment will begin.

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


1900s
1902Theodor Boveri proposes that cancerous tumors arise from single cells that have suffered chromosome damage. He suggests that these chromosome changes cause the cells to divide uncontrollably.
1903S.W. Goldberg and Efim London report the first use of radiation therapy to cure cancer. They describe two patients with basal cell carcinoma of the skin who were cured by radium therapy.
1904Hugh Young and William Halsted perform the first radical perineal prostatectomy to treat prostate cancer. In this surgical procedure, the prostate gland is removed through an incision in the area between the scrotum and the anus.
1907The American Association for Cancer Research (AACR) is established.
1909Paul Ehrlich proposes that the immune system usually suppresses tumor formation, a concept that becomes known as the “immune surveillance” hypothesis. This proposal will stimulate research aimed at harnessing the power of the immune system to fight cancer, including the development of cancer vaccines.
1910s
1911Peyton Rous discovers a virus that causes cancer in chickens (Rous sarcoma virus).
1912Cancer cells are grown in the laboratory, establishing the first long-term "tissue culture."
1913

A nationwide organization dedicated to public education about cancer is formed—the American Society for the Control of Cancer, which later becomes known as the American Cancer Society.

1915

Katsusaburo Yamagiwa and Koichi Ichakawa induce cancer in rabbits by applying coal tar to their skin, providing experimental proof that chemicals can cause cancer. The possibility that some chemicals might cause cancer had been proposed more than 150 years earlier, with the publication of John Hill’s observations on the high rate of nasal cancer among chronic users of snuff.

1920s
1922The Public Health Service opens a Special Cancer Investigations Laboratory at Harvard Medical School.
1928George Papanicolaou discovers that cell samples taken from the vagina can reveal the presence of cervical cancer. This breakthrough leads to the development of the Pap test, which will help save countless lives in the future through its ability to detect cancerous and precancerous cells in the cervix.
1930s
1930The National Institute of Health is established by Congress in the Ransdell Act.
1932David H. Patey develops the modified radical mastectomy for breast cancer. In this surgical procedure, the entire breast, axillary lymph nodes, and pectoralis minor muscle behind the breast are removed. The modified radical mastectomy is less disfiguring than the radical mastectomy and will eventually replace the radical mastectomy as a standard treatment option for breast cancer.
1937Legislation signed by President Franklin D. Roosevelt establishes the National Cancer Institute (NCI).

George Keynes is first person to describe the treatment of breast cancer with breast-conserving surgery followed by radiation therapy. After surgery, long needles containing a radioactive source (radium) were inserted throughout the affected breast and near the axillary lymph nodes. A 5-year survival rate of 69 percent was reported for women whose cancer was confined to the breast.

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


1940s
1941Charles Huggins discovers that blocking the production of male hormones by removing the testicles or administering estrogens induces the regression of prostate tumors. This "hormonal therapy" of prostate cancer is still used today.
1943The Pap test is introduced into medical practice. Widespread use of this test in the United States since the 1950s has helped reduce cervical cancer incidence and mortality by more than 70 percent.
1944Oswald Avery, Colin MacLeod, and Maclyn McCarty identify DNA as the basic genetic material of cells.
1945Terrence Millin introduces retropubic prostatectomy, in which the prostate gland is removed through an incision in the lower abdomen. This surgical procedure, which permits the simultaneous removal of regional lymph nodes for better cancer staging, will soon replace perineal prostatectomy as the preferred surgical approach for treating prostate cancer.
1947Sidney Farber demonstrates that aminopterin, a derivative of folic acid, can inhibit the growth of acute leukemia cells. Aminopterin is the first of a class of drugs known as “antimetabolites.” Because they are structurally similar to chemicals needed for normal cellular processes, antimetabolites can interfere with cell growth and proliferation.
1948George Hitchings synthesizes 6-mercaptopurine (6-MP), an antimetabolite that will be used in the treatment of acute leukemia in children and adults.
1949Nitrogen mustard (mechlorethamine) becomes the first chemical agent approved by the Food and Drug Administration (FDA) for the treatment of cancer. Nitrogen mustard belongs to a class of drugs called alkylating agents, which kill cancer cells by chemically modifying their DNA.
1950s
1950Ernst Wynder, Evarts Graham, and Richard Doll identify cigarette smoking as an important factor in the development of lung cancer.
1952Alfred Hershey and Martha Chase show that DNA is the genetic material of a virus called bacteriophage T2. This work also rules out the possibility that proteins function as hereditary material.
1953James Watson and Francis Crick discover the molecular structure of DNA (the double helix).

Carl Nordling proposes that cancer cells contain mutations in a number of different genes and that cancer-inducing mutations accumulate as a person ages—explaining, in part, why cancer is primarily a disease of the elderly. The multi-step nature of carcinogenesis will be confirmed in many later studies.

The FDA approves methotrexate, an antimetabolite derived from folic acid, and 6-mercaptopurine as anticancer drugs.
1955The Cancer Chemotherapy National Service Center (CCNSC) at NCI is created to obtain and test compounds as possible anticancer agents. The CCNSC pioneered the development of methods and tools, such as cell lines and animal models, for chemotherapy drug discovery.

NCI's Clinical Trials Cooperative Group Program is established to test anticancer agents identified in the NCI drug development program. In the future, the Cooperative Group Program will expand its scope to study combination treatments for cancer, methods of cancer prevention and early detection, and interventions to improve the quality of life of cancer patients.

Roy Hertz and Min Chiu Li achieve the first complete cure of a human solid tumor by chemotherapy. The drug methotrexate is used to cure a patient with choriocarcinoma, a rare type of cancer that forms in tissues of the reproductive system and mostly affects women.
1957Alick Isaacs and Jean Lindenmann discover interferon, a virus-fighting protein produced by animal cells. Eventually, three major types (I, II, and III) of interferon will be identified. In addition to fighting virus infections, interferons can also fight tumors.

Charles Heidelberger develops and patents 5-fluorouracil (5-FU), an antimetabolite that becomes widely used in cancer chemotherapy.
1958NCI researchers Emil Frei and James Holland and their colleagues pioneer the use of combination chemotherapy, in which multiple drugs with different mechanisms of action are used together. Partial and complete remissions, as well as prolonged survival, are obtained in children and adults with acute leukemia treated with combinations of 6-mecaptopurine and methotrexate.
1959The FDA approves the drug cyclophosphamide, a nitrogen mustard alkylating agent, for the treatment of cancer. Cyclophosphamide is designed to be inactive until it is taken up by cells, where it is metabolized to the active form. This type of drug is called a pro-drug.

150 Years of Advances Against Cancer - 1960s


1960s
1960Peter Nowell and David Hungerford describe the first consistent chromosome abnormality in human cancer—an unusually small chromosome in the cancer cells of patients with chronic myelogenous leukemia (CML). This chromosome becomes known as the Philadelphia (Ph) chromosome in honor of the city in which it was discovered.

Howard Temin proposes the DNA provirus hypothesis of cancer. He suggests that DNA copies of some RNA viruses, known as retroviruses, can be inserted into the DNA of infected cells and contribute to the development of cancer.
1961Marshall Nirenberg and Heinrich Matthaei demonstrate that the information to make proteins is stored in the triplet nucleotide code of DNA.

The FDA approves vinblastine for the treatment of cancer. Vinblastine binds to the protein tubulin, the basic building block of microtubules, which are fibrous structures inside cells that play a key role in cell division. This drug is a plant alkaloid originally obtained from the Madagascar periwinkle (Catharanthus roseus, formerly known as Vinca rosea).
1962The Royal College of Physicians issues a report that identifies cigarette smoking as a cause of lung cancer and bronchitis, as well as a likely contributor to the development of heart disease.

The FDA approves 5-FU for the treatment of cancer.
1963The FDA approves vincristine, a drug related to vinblastine, for the treatment of cancer.

Charles Moertel, Richard Reitemeier, and Robert Gage report results of the first placebo-controlled trial of antiemetic drugs to treat chemotherapy-induced nausea and vomiting. The drugs thiopropazate and prochlorperazine are found to be more effective than placebo.

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.

Bergein Overholt begins clinical testing of a flexible fiber-optic sigmoidoscope for the examination of the inside of the lower colon.
1964The 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. According to the report, cigarette smoking can shorten human life, cause lung and other cancers, and play a role in the development of chronic bronchitis, emphysema, and heart disease.

For the first time, a virus—the Epstein-Barr virus—is linked to human cancer (Burkitt lymphoma).

The American Society of Clinical Oncology (ASCO) is established.
1965More than 42 percent of U.S. adults report that they smoke tobacco regularly.
1966NCI standardizes the testing of cancer-causing chemicals.
1967The guaiac fecal occult blood test (FOBT) is introduced as a screening test for colorectal cancer. Guaiac is a resin obtained from the tree Guaiacum officinale and is used to detect heme, the iron-containing part of the blood protein hemoglobin, in stool samples.
1968 Robert Yuan and Mathew Meselson purify an enzyme known as a restriction endonuclease from the bacterium Escherichia coli and show that it cuts (or restricts) the chromosome of a bacterial virus at a specific DNA sequence. In subsequent years, numerous additional restriction endonucleases, each of which cuts DNA at a unique nucleotide sequence, will be purified from E. coli and other bacteria. These enzymes will become vital tools in DNA analysis and cloning.
1969 Robert Huebner and George Todaro propose the oncogene hypothesis of cancer. According to this hypothesis, oncogenes are genes that have the potential to make cells become cancerous. They arise by mutation or increased expression of certain normal genes, which are called proto-oncogenes.

William Wolff and Hiromi Shinya perform the first complete examination of the colon using a flexible fiber-optic device. These researchers are soon able to perform routine full-length colonoscopies using a 186-centimeter-long flexible colonoscope.

150 Years of Advances Against Cancer - 1970s


1970s
1970Howard Temin and David Baltimore discover the enzyme reverse transcriptase (RT). RT synthesizes complementary DNA copies of RNA templates and will soon become an important tool in cancer research.

Congress passes the Public Health Cigarette Smoking Act, which bans the advertising of cigarettes on television and radio beginning January 2, 1971.

The prevalence of U.S. adult smoking declines to 37.4 percent.
1971Alfred Knudson proposes the “two-hit” mutation hypothesis for the development of retinoblastoma, a cancer of the eye that mainly affects children under the age of 6. He suggests that retinoblastoma is caused by two genetic mutations, one that is inherited and one that occurs after birth. This hypothesis is consistent with the multi-step nature of carcinogenesis originally proposed by Carl Nordling in 1953.

President Richard M. Nixon converts the Army's former biological warfare facilities at Ft. Detrick, Maryland, to laboratories for research on the causes, treatment, and prevention of cancer.

Cisplatin, a platinum-containing anticancer compound, enters clinical trials.

President Richard M. Nixon signs the National Cancer Act of 1971 on December 23. This Act authorizes the NCI Director to coordinate all activities of the National Cancer Program, to establish national cancer research centers, and to establish national cancer control programs.

Godfrey Hounsfield and James Ambrose perform the first computed tomography (CT) scan of a human patient—a woman with a suspected brain tumor.
1973NCI’s Surveillance, Epidemiology, and End Results (SEER) program is established to collect and analyze data on cancer incidence, prevalence, and mortality in the United States.

Certifications in medical oncology and gynecologic oncology are offered for the first time.

The inventor Dean Kamen develops the first portable drug infusion pump.
1974The FDA approves doxorubicin, an anthracycline antibiotic from Streptomyces bacteria, for the treatment of cancer.

Michael Hoffman, Edward Phelps, and their colleagues construct a whole-body positron emission tomography (PET) scanner for human studies. The results of initial studies with patients are reported in 1976.
1975Hybridoma technology is developed for the production of monoclonal antibodies. Monoclonal antibodies will become important tools in cancer research and treatment.

Clinical use of flexible sigmoidoscopy for the diagnosis of colorectal disease begins.

Edwin Southern describes a method for transferring fragments of DNA that have been separated by gel electrophoresis on the basis of size to a filter membrane and then localizing specific nucleotide sequences on the membrane by hybridization with complementary DNA probes. This technique, eventually known as “Southern blotting,” will become an important tool in cancer research and lay the foundation for the development of DNA microarray technology.

The Society for Surgical Oncology and the Oncology Nursing Society are established.
1976The results of a randomized clinical trial show that women with early breast cancer who receive post-operative (adjuvant) combination chemotherapy with the drugs cyclophosphamide, methotrexate, and 5-FU have improved disease-free survival.

Dominique Stehelin, Harold Varmus, J. Michael Bishop, and Peter Vogt discover that the DNA of normal chicken cells contains a gene that is related to the oncogene of avian sarcoma virus, which causes cancer in chickens. The researchers suggest that the chicken gene may regulate normal cell growth and development, as well as the malignant transformation of cells in response to physical, chemical, or viral agents. Related DNA will later be identified in human cells. The human gene, c-Src, represents the first human proto-oncogene identified.

Interleukin-2 is discovered in mice. This protein, an immune system cytokine (a hormone-like substance), plays a role in T lymphocyte development and will later be used in cancer therapy.

NCI's Cancer Information Service (1-800-4-CANCER) begins operation.
1977Raymond Damadian, Larry Minkoff, and Michael Goldsmith perform the first magnetic resonance imaging (MRI) examination of a human.

Allan Maxam and Walter Gilbert describe the first efficient method to determine the nucleotide sequence of DNA.

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 will later become known as the Physician Data Query (PDQ) database.
1978The first human testing of a biological therapy for cancer—interferon alpha (a type I interferon)—is conducted.

Tamoxifen, an anti-estrogen drug, is approved by the FDA for the treatment of breast cancer.

Metastatic cancer cells are shown to arise from pre-existing subpopulations of cells in primary tumors.

The FDA approves cisplatin for use in combination with other drugs in the treatment of metastatic testicular cancer and metastatic ovarian cancer.
1979The tumor suppressor gene p53 is discovered. Tumor suppressor genes are genes whose protein products help control cell growth. The p53 gene is the most frequently mutated gene in human cancer.

Harry Towbin, Theophil Staehelin, and Julian Gordon describe a method for transferring proteins that have been separated by gel electrophoresis on the basis of size to a nitrocellulose filter that can then be probed with antibodies to detect individual proteins. This technique, known as “Western blotting,” will become an important tool for cancer researchers.

150 Years of Advances Against Cancer - 1980s


1980s
1980NCI scientist Robert Gallo and his colleagues isolate human T-cell lymphotrophic virus 1 (HTLV-1). This virus, also called adult T-cell leukemia virus, causes adult T-cell leukemia/lymphoma (ATLL) and several other diseases.

Fluorescence in situ hybridization (FISH) is developed. This technique allows researchers to use fluorescently labeled nucleic acid probes to study the chromosomal location and copy number of genes inside cells.

NCI researcher Mark Greene and his colleagues describe a new syndrome, dysplastic nevus syndrome, in melanoma-prone families. Later work will show that dysplastic nevi, which are moles that look different from common moles, are precursors not only of hereditary melanomas but also of melanomas that develop in people without a family history of the disease.

The prevalence of U.S. adult smoking declines to 33.2 percent.
1981The first human cancer prevention vaccine is introduced—the hepatitis B virus vaccine to prevent liver cancer.

A randomized clinical trial in the United Kingdom shows, for the first time, that the rates of survival, local recurrence, and tumor metastasis among women whose breast cancer is treated with modified radical mastectomy are not substantially different from those of women who are treated with radical mastectomy.
1982The first major DNA sequence databases are established, in the United States (GenBank) and Germany.

Scientists report the cloning of an oncogene from human bladder cancer cells. This oncogene, a mutated form of the proto-oncogene Ha-RAS1, is the first human oncogene to be cloned.

NCI's PDQ cancer information database goes online. The PDQ cancer treatment information summaries and clinical trials registry are made available through a dial-up connection to the U.S. National Library of Medicine.
1983Patrick Walsh and his colleagues introduce nerve-sparing retropubic prostatectomy, a form of prostate cancer surgery designed to preserve sexual potency and urinary continence.

Computerized tomography of the colon (also known as virtual colonoscopy) is proposed as a screening method to identify colon polyps and colorectal cancer.

Severe combined immunodeficient (SCID) mice are first described. These mice are deficient in B and T lymphocyte function. They will play an important role in cancer research.

NCI launches the Community Clinical Oncology Program (CCOP), which links community-based physicians with NCI’s Clinical Trials Cooperative Groups and NCI-designated Cancer Centers for participation in NCI-approved clinical trials. CCOP is designed to bring the advantages of clinical research to cancer patients in their own communities.
1984The human p53 gene is cloned.

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.

The association of DNA polymorphisms (normal genetic variants) with cancer risk is first described. Some DNA polymorphisms are associated with an increased risk of cancer, whereas others are associated with decreased risk.
1985Results of a randomized clinical trial show that breast-conserving surgery (lumpectomy) followed by external-beam radiation therapy is equivalent to mastectomy in treating early breast cancer.

The polymerase chain reaction (PCR) technique is introduced. This technique allows millions of copies of a segment of DNA to be made from a single original copy. PCR becomes an important tool in DNA analysis and cloning.
1986The human HER2 proto-oncogene is cloned. HER2 is also called neu and erbB2. Overexpression of the HER2 protein occurs in about 20 to 25 percent of breast cancers (called HER2-positive breast cancers) and is associated with more aggressive disease and poor prognosis.
1987Stephen Friend, Robert Weinberg, and their colleagues report that they have cloned the human retinoblastoma (RB) gene, which is identified as a tumor suppressor gene.
1988Results of a randomized clinical trial show that adjuvant chemotherapy increases the survival of patients with operable colon cancer.

Results of the first randomized clinical trial comparing patient-controlled and continuous infusion of the opioid hydromorphone in the treatment of cancer pain are reported. The effectiveness and toxicity of the two methods of delivering cancer pain medication are found to be similar.

The Bethesda System Conference develops a system for the standard reporting of Pap test results.
1989Carboplatin, a drug related to cisplatin, is approved by the FDA for the treatment of cancer.

150 Years of Advances Against Cancer - 1990s


1990s
1990 Eric Fearon and Bert Vogelstein define the multi-step nature of colon carcinogenesis. They find that the mutation of more than one gene is required for a colon cell to become cancerous.

The prevalence of U.S. adult smoking declines to 25.5 percent.
1991Results of a randomized clinical trial show that adjuvant radiation therapy and chemotherapy improve the survival of patients with rectal cancer.

Two colony-stimulating factors (G-CSF and GM-CSF), which stimulate the growth and development of white blood cells, are approved by the FDA to treat the loss of neutrophils (neutropenia) caused by cancer chemotherapy.

Ondansetron is approved by the FDA to treat nausea and vomiting induced by cancer chemotherapy.

Stephen Fodor and his colleagues develop the technology to produce DNA and protein microarrays. DNA microarrays, which can be used to measure the expression levels of thousands of genes at the same time and to detect single-nucleotide polymorphisms (SNPs) in DNA, become important tools in cancer research.
1992The Mammography Quality Standards Act is passed by Congress. The Act, which will become effective in 1994, requires mammography facilities across the United States to meet uniform quality standards.

Paclitaxel, the first of a class of drugs known as taxanes, is approved by the FDA for the treatment of advanced ovarian cancer. Originally purified from the bark of the Pacific yew tree (Taxus brevifolia), paclitaxel stabilizes microtubules and interferes with cell growth and division. However, rapidly dividing cells, such as cancer cells, are particularly sensitive to the toxic effects of this drug.
1993The results of a randomized controlled trial show that annual screening with FOBT substantially reduces colorectal cancer mortality.

An NCI-convened international workshop on screening for breast cancer reports that screening with mammography reduces breast cancer mortality among women ages 50-69. This conclusion is based on a review of published and unpublished data from eight randomized controlled trials.

The first gene (MSH2) associated with hereditary nonpolyposis colon cancer (HNPCC) is cloned. People with HNPCC are at increased risk of developing colon cancer. The protein produced by MSH2 functions in DNA repair. Later, additional DNA repair genes will be associated with HNPCC.

MicroRNAs (miRNAs) are first identified in the roundworm Caenorhabditis elegans, and their role in regulating gene expression by interfering with the translation of messenger RNAs into proteins is proposed. miRNAs are later found in humans. It has been estimated that the human genome may encode at least 300 different miRNA species, making these non-protein-coding RNAs one of the largest classes of gene regulators identified. Changes in miRNA expression have been associated with many different cancers.
1994The BRCA1 gene is cloned. Women who inherit specific mutations in this gene have greatly increased risks of breast and ovarian cancer.

Human herpesvirus 8 (HHV-8), which causes Kaposi sarcoma, is identified. HHV-8, also known as Kaposi sarcoma-associated herpesvirus (KSHV), will later be linked to primary effusion lymphoma and multicentric Castleman disease.
1995The BRCA2 gene is cloned. Women who inherit specific mutations in this gene have greatly increased risks of breast and ovarian cancer.

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 photosensitizing drug that can be absorbed by tumors, is approved by the FDA for the photodynamic therapy of some types of cancer. When photosensitizing drugs are exposed to light of a specific wavelength, they become active and kill cancer cells.

Information in NCI's PDQ database becomes available on the World Wide Web via the NCI Web site CancerNet.
1996The first sustained decline in cancer death rates in the United States since record keeping began in the 1930s is reported. NCI, the Centers for Disease Control and Prevention, and the American Cancer Society jointly report that the overall cancer death rate fell by 2.6 percent between 1991 and 1995.

Topotecan, 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 activity 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 I inhibitor—irinotecan—for the treatment of metastatic colorectal cancer.
1997The FDA approves the first biotechnology product to treat patients with cancer—a monoclonal antibody called rituximab. Rituximab is initially approved for the treatment of non-Hodgkin lymphoma (NHL) that is resistant to other treatments, but it will later be approved for use as a first-line treatment for several types of NHL.

NCI scientists and their Chinese collaborators find that occupational exposure to the chemical benzene is associated with increased risks of acute non-lymphocytic leukemia and related myelodysplastic syndromes as well as NHL.

The National Cancer Advisory Board recommends that NCI advise all women age 40 years or older to receive screening mammograms every 1 to 2 years.

Cancer stem cells are first identified, in acute myelogenous leukemia (AML). They will later be identified in additional cancer types, including cancers that form solid tumors. Cancer stem cells in solid tumors are the only cells that have the ability to initiate new tumors.
1998Results from the NCI-sponsored Breast Cancer Prevention Trial show that the drug tamoxifen reduces the incidence of breast cancer by 50 percent among women who are at increased risk of the disease. The FDA subsequently approves tamoxifen for the prevention of breast cancer in high-risk women.

Trastuzumab, a monoclonal antibody that targets cancer cells that overproduce the protein HER2, is approved by the FDA for the treatment of metastatic breast cancer.
1999The Hybrid Capture II HPV DNA test is approved by the FDA for use in conjunction with the Pap test in cervical cancer screening.

150 Years of Advances Against Cancer - 2000s


2000s
2000NCI establishes the Center to Reduce Cancer Health Disparities (CRCHD) as part of a major national commitment to identify and address the underlying causes of disease and disability in racial and ethnic communities.

The prevalence of U.S. adult smoking declines to 23.3 percent.
2001The drug imatinib mesylate 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.

Initial findings from the Human Genome Project are reported. Results of the genomic analyses and the advanced DNA sequencing technologies developed during this project will facilitate future projects aimed at investigating the genomic changes that occur in human cancers.
2002NCI launches the National Lung Screening Trial (NLST) to determine whether low-dose helical computed tomography (CT), which is also known as spiral CT, is better than single-view chest x-rays in helping to reduce deaths from lung cancer among current and former heavy smokers.

The International Agency for Research on Cancer (IARC) publishes a monograph on tobacco smoke and involuntary smoking (secondhand smoke) that classifies secondhand smoke as carcinogenic to humans.
2003Results from the NCI-sponsored Prostate Cancer Prevention Trial (PCPT) show that men taking the drug finasteride, which reduces the production of male hormones, were 25 percent less likely to develop prostate cancer than men taking a placebo, demonstrating that prostate cancer can be prevented.

An NCI-supported international clinical trial finds that the drug letrozole lowered the risk of breast cancer recurrence in postmenopausal women diagnosed with early-stage breast cancer who took the drug after completing an initial 5 years of adjuvant therapy with tamoxifen. Letrozole is an aromatase inhibitor, a class of drugs that inhibit the production of the female hormone estradiol.

The FDA approves the drug bortezomib for the treatment of multiple myeloma. Bortezomib represents a new class of targeted agents that inhibit proteasomes, structures inside cells that degrade proteins.
2004Letrozole is approved by the FDA for the adjuvant treatment of early-stage breast cancer in postmenopausal women who have already been treated with 5 years of tamoxifen therapy.

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. The results also show that menopausal hormone therapy with estrogen alone has no benefit in disease prevention, specifically in reducing the risks of colorectal cancer, coronary heart disease, and dementia.

The monoclonal antibody bevacizumab is approved by the FDA for use with other drugs in the treatment of metastatic colorectal cancer. Bevacizumab blocks the activity of a protein called vascular endothelial growth factor (VEGF), which stimulates the growth of new blood vessels to tumors (a process called tumor angiogenesis). Without an adequate blood supply, tumors cannot get the oxygen and nutrients they need for continued growth.

The monoclonal antibody cetuximab is approved by the FDA for the treatment of metastatic colorectal cancer. Cetuximab inhibits the activity of a protein called epidermal growth factor receptor (EGFR), which is overexpressed in some cancers.

The FDA approves oxaliplatin, a platinum-containing drug, for use in the treatment of advanced colorectal cancer.

Palifermin is approved by the FDA to decrease the incidence and duration of severe oral mucositis (painful inflammation and sores in the mouth) in patients with leukemia, lymphoma, or multiple myeloma who have been treated with high doses of chemotherapy and radiation therapy followed by bone marrow or peripheral blood stem cell transplantation.

Results from two randomized clinical trials show that treatment with the drug docetaxel (a taxane) can increase the survival of men with metastatic hormone-insensitive prostate cancer.
2005Results from two large NCI-sponsored randomized clinical trials show that patients with early-stage HER2-positive breast cancer who were treated with the monoclonal antibody trastuzumab in combination with adjuvant chemotherapy had about a 50 percent lower risk of cancer recurrence than patients who received the same chemotherapy without trastuzumab.

NCI and the National Human Genome Research Institute (NHGRI) announce the launch of The Cancer Genome Atlas (TCGA) project, a collaborative effort that, in its initial phase, will systematically explore the genomic changes in lung, brain (glioblastoma), and ovarian cancer. The number of cancers to be studied will later be increased to more than 20.

The FDA approves an albumin-stabilized nanoparticle formulation of paclitaxel for use in the treatment of metastatic or recurrent breast cancer.

The FDA approves the aromatase inhibitors anastrozole and exemestane for the adjuvant treatment of hormone receptor-positive early-stage breast cancer.
2006Initial results from an NCI-sponsored trial, the Study of Tamoxifen and Raloxifene (STAR), show that the drug raloxifene, an antiestrogen used to prevent osteoporosis in postmenopausal women, reduces the incidence of breast cancer in postmenopausal women at increased risk of the disease to the same extent (approximately 50 percent) as tamoxifen. However, raloxifene 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 with the two types of HPV that cause approximately 70 percent of all cases of cervical cancer worldwide. Gardasil also provides protection against the two types of HPV that are responsible for 90 percent of all cases of genital warts. NCI scientists developed the underlying technology used to make Gardasil.

The U.S. Surgeon General releases a report on the harmful health consequences of involuntary exposure to tobacco smoke (secondhand smoke).

The FDA approves trastuzumab for use with other drugs in the adjuvant treatment of women with early-stage node-positive HER2-overexpressing breast cancer.

The FDA approves the drugs thalidomide and lenalidomide, which is a thalidomide derivative, for the treatment of patients with multiple myeloma. Thalidomide is a tranquilizer and antiemetic that was used initially to prevent morning sickness in pregnant women. It was withdrawn from the market in the early 1960s after it was found to cause birth defects.
2007Results of a randomized 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.

Scientists find that the decline in use of menopausal hormone therapy that occurred after the announcement of results from the WHI study was associated with a reduction in breast cancer incidence.

The prevalence of U.S. adult smoking declines to 19.8 percent.
2008Results from a large multicenter study sponsored by NCI show that the accuracy of virtual colonoscopy is similar to that of fiber-optic colonoscopy in detecting intermediate-size and large colorectal polyps, suggesting that the procedure could serve as an initial screening exam for colorectal cancer.

The first TCGA results are announced—findings from a large-scale study of the brain tumor glioblastoma multiforme. The findings include the identification of three previously unknown mutations in this disease and the identification of core cell-signaling pathways that are disrupted in this type of brain cancer.

The prevalence of U.S. adult smoking increases to 20.6 percent.
2009The FDA approves Cervarix, a second vaccine that protects against persistent infection with the two types of HPV that cause approximately 70 percent of all cases of cervical cancer worldwide.

Formaldehyde is associated with increased risks of cancers of the blood and lymphatic system in workers exposed occupationally to this chemical.
2010The FDA approves the use of sipuleucel-T for the treatment of metastatic hormone-insensitive prostate cancer. Sipuleucel-T is the first approved human cancer treatment vaccine.

Results of a randomized clinical trial show that the drug cabazitaxel can increase the survival of men with metastatic hormone-insensitive prostate cancer whose disease has progressed despite treatment with the drug docetaxel.

Results of a randomized controlled trial in the United Kingdom show that one-time screening of people between the ages of 55 and 64 with flexible sigmoidoscopy can help reduce colorectal cancer incidence and mortality.

Initial results of NLST show that screening with low-dose helical CT can help reduce lung cancer deaths among current and former heavy smokers.