Download After the Act: 25 Years of Advances Against Cancer

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tary interventions, including genetically
engineered foods that block or delay the
onset of malignancy.
Also, genetic testing will usher in
the ability to identify people at especiallv hieh or low risk of cancer — an
advance that
carries both
the enormous
potential to
improve human health
and the risk of
abuse. Those
at low risk for
'f y f i cancer may be
*' spared rempeated and
Dr. Arnold Levlne
costly screenings, while those at high risk may be
monitored closely enough that nontoxic
preventive agents can stop incipient cancers from ever developing. However,
high-risk individuals may also suffer genetic discrimination unless legal and
ethical safeguards are firmly in place.
Challenges
The good news about cancer during
the next quarter-century is also tempered by other obstacles looming in the
future, including funding threats to the
cancer effort and the difficulty of applying the benefits of the National Cancer
Program to everyone. If these challenges are not met, experts say, the scientific advances of the past 25 years
will not be translated into large, measurable gains against cancer incidence and
mortality in the U.S. population.
In spite of the wealth of new knowledge generated since 1971, support for
basic research needs to continue, observers say. "We owe an enormous debt
in cancer research to fundamental yeast
genetics and analysis of the cell cycle,"
1796 NEWS
After the Act: 25 Years of Advances
Against Cancer
The past quarter-century has seen remarkable advances against cancer, many coming as
a direct or indirect result of passage of the National Cancer Act in 1971. Among them:
Cancer Mortality Rates:
• Overall cancer death rates fell 2.6% from 1991 to 1995
• Lung cancer death rates for men fell 6.7% from 1991 to 1995
• Death rate for colorectal cancer dropped 17% since 1973
• Death rate for breast cancer dropped 7.7% from 1989 to 1995
• Testicular cancer death rate dropped 66% since 1973
• Hodgkin's disease death rate dropped 57% since 1973
• Death rate for childhood leukemia is down 52% since 1973
Technologies:
• Recombinant techniques developed for cloning genes, mid-1970s
• Hybridoma technology for monoclonal antibodies developed, 1975
• Southern blot technique to identify DNA fragments developed, 1975
• Methods developed to sequence DNA fragments, 1975 to 1976
• First biotechnology firm (Genentech) founded, 1976
• Restriction fragment length polymorphism technique used in cancer, 1983
• Polymerase chain reaction technique developed, mid-1980s
• Severe combined immunodeficiency (SOD) mice developed, mid-1980s
• Fluorescence in situ hybridization (FISH) technique developed, about 1990
Cancer Genetics:
• First (src) of some 50 now-known human proto-oncogenes discovered, 1976
• Most frequently mutated gene in human cancer, p53, discovered, 1979
• First (RB1) of some 20 now-known tumor suppressor genes cloned, 1986
• First human gene therapy for cancer (melanoma), 1991
• First (hMSH2) of the hereditary nonpolyposis colon cancer genes cloned,
1993
• BRCA1 and BRCA2 inherited breast cancer genes cloned, 1994 and 1995
Epidemiology:
• Surveillance, Epidemiology, and End Results (SEER) Program established, 1973
• Development of logistic regression statistics for multiple variables
• Integration of biochemical assays into epidemiologic studies (molecular epidemiology)
Treatment:
• Interleukin-2 discovered, 1976
• First human testing of a biological therapy (oc-interferon), 1978
• Adjuvant therapies shown to improve disease-free survival in early breast cancer, 1978
• First human cancer vaccine (hepatitis B virus vaccine, for liver cancer), 1981
• Community Clinical Oncology Program established, 1983
• Breast-sparing surgery replaced Halsted radical mastectomy for breast cancer, 1985
• Modified prostatectomy to preserve potency developed, 1986
• Adjuvant chemotherapy found to increase survival in colon cancer, 1989
• Adjuvant radiation and chemotherapy found to improve survival in rectal cancer, 1991
• Computerized pain medication infusion pumps developed
• Combination chemotherapies proven effective
Journal of the National Cancer Institute, Vol. 88, No. 24, December 18, 1996
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Cancer Concepts:
.<
• Established that proto-oncogenes play roles in normal cell cycle control, 1970s
• Cytochrome P450 enzyme system shown to activate many carcinogens, 1970s
• Metastatic cells shown to arise from subpopulations in primary tumors, 1978
• Multistep nature of carcinogenesis proven by 1990
Prevention:
• Prevalence of adult cigarette smoking dropped from 37% in 1971 to 24% in 1993
• Dietary guidelines to reduce cancer developed, 1984
• First chemoprevention trial reported showing efficacy (vitamin A analogue against
mouth and throat tumors), 1990
• ASSIST, largest tobacco prevention and control project in U.S., launched, 1991
• NCI-sponsored studies in China show importance of nutrition in preventing cancer,
1991.
Detection and Diagnosis:
• Computed tomography introduced to the United States, 1973
• Positron emission tomography (PET) developed, mid-1970s
• Flexible sigmoidoscope developed, 1980
• Magnetic resonance imaging (MRI) introduced, early 1980s
• Bethesda System conference developed system for reporting Pap smear results, 1988
• Mammography Quality Standards Act passed, 1992
• Transition from film-based radiology to digital computer-assisted medical imaging
• Transition from gross anatomic imaging to visualizing tissue and cell function
• Transition from noninvasive imaging to image-guided biopsy and treatment
Anticancer Drugs (year of FDA approval):
• Doxorubicin(1974)
• Cisplatin (1978)
•Tamoxifen(1978)
• Levamisole (1990)
•Paclitaxel(1992)
•Topotecan(1996)
• Drug analogues developed that offer greater patient convenience and slightly less
toxicity
Information Transfer:
• Cancer Information Service (1-800-4-CANCER) opened, 1976
• First national cancer patient education program (I Can Cope) founded, 1977
• PDQ (Physician Data Query) established, 1982
• First major DNA sequence databases established, in United States (GenBank) and
Germany, 1982
• Human Gene Mapping database established, 1989
Cancer Specialists:
• Certification in medical oncology (6,550 now certified) first offered, 1973
• Certification in gynecologic oncology (559 now certified) first offered, 1973
• Society for Surgical Oncology (1,600 members now) established from earlier group,
1975
• Oncology Nursing Society (24,000 members now) established, 1975
• Certification in radiation oncology (3,130 now certified), 1989
• Compiled from various sources by Hugh Mclntosh
Journal of the National Cancer Institute, Vol. 88, No. 24, December 18, 1996
Levine explained. "If for any reason the
support for inquiry and funding for research in those areas is shut off prematurely or is not realized to be as
important, it will retard the progress of
cancer research."
Freeman, noting that $2.4 billion a
year— 10 times as much as in 1971 —
is now being infused into the National
Cancer Program — is confident that financial support will continue. "That
does not seem to be a major problem at
this point," he said.
Clinical Research
But he points to the upheaval in the
country's health care system and the
threat it poses
to clinical research.
"What we're
seeing now is
a great challenge to the
war against
cancer, if
something
isn't done to
somehow assure that cliniDr. Harold P. Freeman
c a [ research
• • • & ' •
money is still supplied," Freeman said.
Traditionally, patients' health insurance covered much of the cost of their
participation in clinical research. But
as health insurers have become more
competitive, particularly those in the
managed care industry, they have increasingly seen clinical research and
training as outside their responsibility. A new way of paying for these activities will have to be developed,
experts suggest, and that mechanism
will likely be some sort of government funding.
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