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Fox Chase Cancer Center's Dr. Alfred G. Knudson Honored by American Society of Pediatric Hematology/Oncology

PHILADELPHIA (September 27, 1999) — Dr. Alfred G. Knudson, a Fox Chase Cancer Center Distinguished Scientist and senior advisor to the Center president, has received the 1999 Distinguished Career Award of the American Society of Pediatric Hematology/Oncology. The ASPHO honor, presented Sept. 17 at the organization's annual meeting in Montreal, is the latest award recognizing Knudson's seminal work in explaining how genetic mutations lead to both hereditary and nonhereditary cancers.

The recipient of the 1998 Albert Lasker Award in Clinical Medical Research, Knudson has received commendation from learned societies around the world for his "two-hit" theory of cancer causation. It provided a unifying model for understanding how cancer develops.

Starting with studies of children with retinoblastoma, a cancer of the eye, he found that children who developed the cancer in both eyes did so at younger ages than children with one affected eye. The patients whose cancer affected both eyes proved to have a hereditary susceptibility to the disease. Those who survived and had children of their own passed on this susceptibility to 50 percent of their children.

The mathematical models Knudson developed indicated that two gene-altering events-two "hits," or mutations-are necessary to bring about the cancer. Those with the hereditary susceptibility inherited a gene defect at conception. Since cells have two copies of each gene, the remaining normal copy can protect against a specific cancer unless that gene, too, develops a mutation.

Long before the tools existed to confirm his ideas, Knudson also postulated that such genes may function as tumor suppressors unless they are altered. Proof of Knudson's theories came in 1986 with the discovery of the retinoblastoma gene by Dr. Stephen H. Friend, now director of molecular pharmacology at Fred Hutchinson Cancer Research Center. An important gene during early embryonic development, it normally functions as a tumor-suppressor gene later in life.

The ASPHO award is special to him, Knudson explained, because it represents a tribute from his peers and one-time colleagues. "There was a wonderful article in the ASPHO journal that included some really gratifying comments from several people."

In the guest commentary on Knudson in the July-August 1999 issue of The Journal of Pediatric Hematology/Oncology, Dr. Giulio J. D'Angio of the radiation oncology department at the University of Pennsylvania included remarks from other distinguished researchers around the world. They said, in part:

"What some people may know, but few appreciate, is the depth of the thinking that went into Al Knudson's two-hit model for carcinogenesis," said Stephen Friend. "...His model, which went far beyond the epidemiological and molecular biology studies that would come later, crystallized the fundamental theories that underlie the awareness of tumor-suppressor genes as they are known and studied today...."

"Al's very thoughtful analysis of the pattern of inheritance of retinoblastoma led to the development of a new paradigm, the validity of which is still apparent almost 30 years later...," said Dr. Janet D. Rowley, professor of medicine and molecular genetics at the University of Chicago.

"I came across Knudson's two-hit hypothesis during my first job in pediatrics [and] was struck immediately by the simplicity of his idea-this was where cancer biology could meet the patient, the original translational research," said Dr. Kathryn Pritchard-Jones of the Institute of Cancer Research and Royal Marsden Hospital in London, England. "...It is a great and fitting tribute to Al's insight into a clinical problem that his ideas, first formulated in the late 1960s, paved the way for the next 30 years of cancer research and beyond."

"It is through his concept of a two-hit model of tumorigenesis that the molecular basis of inherited cancer is now well-established," said Dr. Anthony Reeve, director of the Cancer Genetics Laboratory at Otago University in Dunedin, New Zealand.

Born in Los Angeles in 1922, Knudson received his bachelor of science degree from California Institute of Technology in 1944, his M.D. from Columbia University in 1947 and his Ph.D. from California Institute of Technology in 1956. He held a Guggenheim fellowship from 1953 to 1954.

Knudson came to Fox Chase from the University of Texas Graduate School of Biomedical Sciences, where he was dean, and the M. D. Anderson Hospital and Tumor Institute in Houston, Texas, where he specialized in pediatrics and biology. Previously, he was associate dean for basic sciences at the State University of New York at Stony Brook from 1966 to 1969.

He began his affiliation with Fox Chase in 1970 as a member of its scientific advisory committee and joined the Center staff in 1976. He served as director of the Center's Institute for Cancer Research until 1983, Center president from 1980 to 1982 and scientific director from 1982 to 1983. For the past 10 years, Knudson was an instrumental leader in the molecular oncology program at Fox Chase. The Center named him a Fox Chase Distinguished Scientist in 1992.

Fox Chase Cancer Center is one of 36 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.

The American Society of Pediatric Hematology/Oncology is a multidisciplinary professional organization of more than 800 specialists in the treatment of childhood cancer and blood disorders. The society is dedicated to promoting optimal care of children and adolescents with blood disorders and cancer by advancing research, education, treatment and professional practice.

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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