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A Fox Chase Cancer Center Pioneer in Cancer Research To Receive Nation's Most Distinguished Honor

PHILADELPHIA (September 1, 1998) -- Fox Chase Cancer Center is proud to announce Alfred G. Knudson, Jr., M.D., Ph.D., will receive a 1998 Albert Lasker Medical Research Award, Friday, September 25. The Lasker Award is the nation's most distinguished honor for outstanding contributions to basic and clinical medical research. It will be presented at a luncheon in New York City.

The Lasker Awards were first presented in 1946. Often called "America's Nobels," 59 Lasker Award recipients have subsequently received the internationally renowned Nobel Prize. An international jury of top medical researchers annually selects the Lasker Award recipients, thereby contributing to the distinction conferred by the Awards. The Albert & Mary Lasker Foundation administer the Lasker Awards. The late Mary Lasker is widely recognized for her singular contribution to the growth of the National Institutes of Health, and her commitment to the cause of biomedical research.

Dr. Knudson will receive the Albert Lasker Clinical Research Prize, awarded for the original demonstration that cancer in humans has a genetic basis caused by rearrangements in the chromosomes or mutations in individual genes.

Knudson, Peter C. Nowell, M. D., of the University of Pennsylvania School of Medicine and Janet D. Rowley, M.D., of the University of Chicago share the award.

One of the most significant achievements of molecular genetics in the past few years has been the identification of a number of tumor-suppressor genes that, when mutated, lose their ability to control cell division. Malignancy is the result.

Explaining why some tumors are hereditary and others appear to be "sporadic" was one of the great conundrums of cancer biology until Dr. Knudson came up with the "two-hit" hypothesis. It provided a unifying model for understanding cancer that occurs in individuals who carry a "susceptibility gene" and cancers that develop because of randomly induced mutations in otherwise normal genes. Like many significant conceptual leaps in science, Knudson's "two-hit" hypothesis was met with skepticism when he first published it in 1971.

Knudson was studying children with retinoblastoma, a cancer of the eye, noting differences among patients whose tumor was inherited and those who appeared to have no "susceptibility" to the disease.

"Most people assumed that retinoblastoma genes were inherited in a dominant fashion - that is, if you had the gene, you would get the cancer," Knudson said. Since some children who inherit the gene do not get the tumor, it is apparent that inheriting the mutation is not sufficient for tumor formation. The inherited gene is the "first hit," but another hit after conception produces a tumor. The same gene, known as RB1, is involved in children with the non-hereditary form, but these children sustain "two hits" after conception.

The "hits" can occur in many ways - from an environmental toxin, dietary factors, radiation, or the kind of random mutation that sometimes occurs during the intricate process of normal cell replication. Knudson proposed that retinoblastoma develops either because a key gene is lost or because it is inactivated and unable to function as it should.

Knudson, far ahead of his time (and ahead of his own hard data), hypothesized in the early 1970s that some genes' normal role in life is to behave as "tumor-suppressor" genes that keep cell division under healthy control. At first, the strength of his hypothesis rested on a complex mathematical model, but it was supported in 1976 when Knudson and others showed that some patients with retinoblastoma are missing a segment of chromosome 13. In 1986, other scientists applied the tools of molecular technology to clone the gene, RBI, so that its function as a tumor-suppressor could be studied in detail.

Knudson's initial studies were directed at relatively rare tumors. It is now apparent that his "two-hit" hypothesis explains the origin of most common forms of cancer and is one of the defining concepts behind all of modern cancer biology.

Knudson has been a senior member of the scientific research staff at Fox Chase Cancer Center since 1976. In honor of his contributions to biomedical science, Knudson has been elected to the National Academy of Sciences. He was named a Fox Chase Distinguished Scientist and senior advisor to the institution's president in 1992.

Knudson has been instrumental as a leader of Fox Chase's molecular oncology program since 1989. Previously, Knudson served as director of Fox Chase's Institute for Cancer Research until 1982, Center president from 1980 to 1982 and scientific director from 1982 to 1983.

Fox Chase Cancer Center is one of 34 National Cancer Institute-designated comprehensive cancer centers in the nation. The Center's activities include basic and clinical research, prevention, detection and treatment of cancer and community outreach programs.

Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence four consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach.  For more information, call 1-888-FOX CHASE or (1-888-369-2427).

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