tion of other genes could be to inhibit, or suppress,
cancer. In the 1980’s, Knudson was shown to be cor-
rect with the discovery of the first tumor-suppressor
gene, called the retinoblastoma (Rb) gene because
of its role in inherited forms of the eye disease reti-
noblastoma. The genes that encode the Rb protein
and a second tumor suppressor, p53, were cloned
by the end of the decade. The number of tumor-
suppressor genes discovered during the decade ap-
proached two dozen.
The question of how cancer cells remain “immor-
tal” was partly solved during the 1980’s, opening a
possible means for cancer therapy. In the 1960’s,
John Hayflick had discovered that normal cells have
a limited lifespan. In the 1980’s, Elizabeth Black-
burn and her colleagues determined that one rea-
son for cell mortality lies in the shortening of the
chromosomes during each cycle of cell division. The
tips of these chromosomes are capped with short
deoxyribonucleic acid (DNA) sequences called telo-
meres, which serve as buffers against chromosomal
loss. Blackburn discovered telomerases, enzymes that
replace the telomere caps in fetal cells; telomerase
activity shuts down as cells age, eventually resulting
in cell death. It was subsequently discovered that
cancer cells re-express telomerase activity, which al-
lows them to survive and continue to replicate.
Trends in Cancer Pathology Among males during
the 1980’s, cancer rates continued trends that had
begun in previous decades. Perhaps the most sur-
prising of these trends was the significant decrease
in stomach cancer to a level less than 40 percent of
its rate a half century earlier. Lung-cancer rates, on
the other hand, continued to increase, reaching a
mortality level approaching 80 deaths per 100,000
males by the end of the decade. Not surprising, most
of the increase was attributed to cigarette smoking.
Mortality associated with prostate cancer demon-
strated a slight increase, reaching a level of 20 to 25
deaths per 100,000 males.
Among women, many of the same trends were ap-
parent. The most striking change, however, was in
the rate of cancer of the lung and bronchus. Mortal-
ity rates among women had tripled by the end of the
decade, reaching a level of 30 deaths per 100,000 fe-
males and surpassing the mortality rate associated
with breast cancer.
Anticancer Drugs and Treatment The discovery that
certain cancers express unusual surface proteins al-
lowed for the development of drugs that could target
cancer cells by seeking out those proteins. Mono-
clonal antibodies were found to be effective in treat-
ing certain forms of lymphoma, as well as melano-
mas. The efficacy of mastectomy, the removal of a
breast, as a means to eliminate the disease had long
been controversial. A study completed in the 1980’s
found that, in many cases, a lumpectomy—removal
of a tumor from the breast—was as effective as the
more radical procedure for treating the patient.
Impact Prior to the 1980’s, cancer research had
been primarily observational: scientists cataloged
phenomena without understanding the mechanisms
underlying those phenomena. During the 1980’s,
however, the molecular basis of the disease began to
be understood. The role played by cellular proto-on-
cogenes was particularly intriguing. As originally
defined, these genes were shown to regulate the
progress of a cell through its cycle of development,
ultimately resulting in division. In some cases, how-
ever, the same proto-oncogenes that stimulate cell
division may also inhibit the cell cycle, even induc-
ing apoptosis (cell “suicide”), thereby serving as tu-
mor suppressors as well as tumor inducers.
It was during the 1980’s that the first chemo-
therapeutic agents directed against specific forms of
cancer were discovered. The usefulness of mole-
cules such as monoclonal antibodies still remains
limited. However, the discovery that many cancer
cells express specific forms of surface proteins made
“designer” drugs directed against these forms of the
disease practical. Among the drugs subsequently li-
censed was herceptin, an inhibitor of breast-cancer
cells that express the HER receptor, one of the
proto-oncogene products discovered in the 1980’s.
Further Reading
Bishop, J. Michael.How to Win the Nobel Prize.Cam-
bridge, Mass.: Harvard University Press, 2003. Au-
tobiography of the scientist who helped discover
cellular oncogenes.
Coffin, John, et al.Retroviruses.Plainview, N.Y.: Cold
Spring Harbor Laboratory Press, 1997. Story of
retroviruses and the role they played in the dis-
covery of oncogenes.
Pelengaris, Stella, and Michael Khan.The Molecular
Biology of Cancer.Malden, Mass.: Blackwell, 2006.
Extensive discussion of the discovery of oncogenes
and their role in the development of cancer.Gere, Richard
186 Cancer research The Eighties in America