Alfred G. Knudson, Jr., MD, PhD (photo), a pioneering cancer researcher who is internationally recognized for his groundbreaking “two-hit” hypothesis, which helped provide the basis for our current understanding of the genetic origins of cancer passed away on July 10, 2016 at 93 years of age.
“The [...] cancer research world as a whole has lost a true visionary with the passing of Knudson. He proposed the two-hit hypothesis many years before the molecular technologies needed to experimentally test and confirm it were even available,” noted Margaret Foti, PhD, MD, chief executive officer of the American Association for Cancer Research (AACR). “Since then, Knudson’s remarkable research has become the bedrock on which our understanding of cancer biology is built, and it continues to have important implications for future progress against cancer.”
World-renowned cancer geneticist
Knudson was a world-renowned cancer geneticist and physician who treated children with retinoblastoma, a rare type of cancer. He proposed the two-hit hypothesis in 1971 to explain the relationship between the hereditary and nonhereditary forms of retinoblastoma, 15 years before molecular technologies were available to compare genetic differences between tumors in patients with hereditary versus sporadic cancers. 
The two-hit hypothesis predicted the existence of tumor suppressor genes that can suppress cancer cell growth. Knudson subsequently mapped the retinoblastoma susceptibility gene to chromosome band 13q14, laying the foundation for the eventual cloning of RB1, the first tumor suppressor gene.
The now-confirmed two-hit hypothesis advanced understanding of the genetic mutations that turn normal cells into cancer cells. It also guided the work of many geneticists and molecular biologists over the years and provided powerful insights into the development of cancer as well as cancer treatment and prevention.
Knudson’s scientific accomplishments have been widely recognized. He was the recipient of the Charles S. Mott General Motors Cancer Research Foundation Prize in 1988, the American Cancer Society Medal of Honor in 1989, the Canada Gairdner International Award in 1997, the Albert Lasker Award for Clinical Medical Research in 1998, the Distinguished Career Award from the American Society of Pediatric Hematology/Oncology in 1999, the Kyoto Prize in 2004, the Bristol-Myers Squibb Freedom to Discover Award for Distinguished Achievement in Cancer Research in 2005, and the AACR Lifetime Achievement Award in 2005. Knudson was elected a member of the National Academy of Sciences in 1992 and was elected an inaugural Fellow of the AACR Academy in 2013.
In 2015, during the American Society of Clinical Oncology (ASCO)'s 50th anniversary celebration, Knudson was honored as an Oncology Luminary. The honor recognizes exceptional individuals who have helped shape the field of oncology and have advanced progress against cancer.
The esteem in which the cancer research community has held Knudson over the many years of his stellar career is highlighted by the fact that the journal Genes, Chromosomes & Cancer devoted its entire December 2003 issue to his work and that he appeared on the cover of AACR’s flagship journal Cancer Research four times.
In addition to his academic and research contributions, Knudson was an active member of the AACR since 1976, serving as associate editor of Cancer Research from 1985 to 2000 and the editorial board of Cancer Epidemiology, Biomarkers & Prevention from 1991 to 1998. Additionally, he was a member of the 2012 AACR Award for Lifetime Achievement in Cancer Research Committee.
Fox Chase Cancer Center
Born in Los Angeles, Aug. 9, 1922, Knudson received his medical degree at Columbia University in New York and his PhD in biochemistry and genetics at the California Institute of Technology in Pasadena. He was a senior member of the scientific research staff at Fox Chase Cancer Center in Philadelphia since 1976, including serving as director of the Fox Chase Institute for Cancer Research from 1976 until 1982, president of Fox Chase Cancer Center from 1980 to 1982, and scientific director of the cancer center from 1982 to 1983.
Beyond his many achievements as a distinguished researcher and renowned leader of the Fox Chase Cancer Center, Knudson was well known for his passionate commitment to mentoring students, fellows, early-career scientists, and senior investigators. His selfless dedication to mentorship helped inspire generations of leaders in the field of cancer research.
Knudson is survived by his wife, Anna Meadows, MD, emeritus member of the AACR and emeritus professor of pediatrics and medicine at the Perelman School of Medicine at the University of Pennsylvania. He is also survived by six children and stepchildren, 10 grandchildren and step grandchildren, and two great grandchildren.
Knudson will long be remembered and sorely missed by all who knew and loved him.
 Knudson AG. Karnofsky Memorial Lecture. Hereditary cancer: theme and variations. J Clin Oncol. 1997 Oct;15(10):3280-7.
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