07/23/04

Genetic Predispositions for Cancers in Humans
Arnold J. Levine, Institute for Advanced Study, Princeton, NJ and The Cancer Institute of New Jersey, New Brunswick, NJ

Lecture Abstract:
By the decade of the 1960’s several different causes of cancer were known but the relationship between these causes remained obscure. An abundance of evidence had demonstrated that viruses, chemicals, genetic alterations and the process of aging could all contribute to the origins of cancers but how these facts could be drawn together in a single unified hypothesis remained unclear. By the 1970’s the discovery of cellular oncogenes in retroviruses began the unification of some of these contributors to cancer and in the 1980’s the identification of tumor suppressor genes made it clear how germ line mutations lead to cancers at young ages. The decade of the 1990’s brought us the elucidation of many signal transduction pathways, composed of oncogenes and tumor suppressor genes that often played a critical role in the development of the organism, and when mutated gave rise to cancers. At the beginning of the 21st century the human genome project provided us with an almost complete list of genes and the genetic polymorphisms in and around these genes that make us different individuals and predispose some to disease processes. Using this information we are now beginning to uncover how single nucleotide polymorphisms in our genome, along with somatic mutations or viruses, can contribute to the origins of cancer in humans. The lecture will demonstrate how combinations of germ line mutations and polymorphisms in the p53 signal transduction pathway, a tumor suppressor gene that responds to external stress, both increase the frequency and decrease the age of onset of cancers. These observations now unify the roles of viruses, chemicals, genes, and aging in the causes of cancers in humans and these conclusions have begun to lead to rational approaches to drug design and the first remissions of cancers without toxicity. We can now see the day when such drugs will be tailored to the genetic background of an individual or a tumor, and positive responses will be observed at higher frequencies. The success of this ration approach in drug design will validate the concepts developed over the past 45 years.

Arnold Levine, Ph.D. is a Professor at the Cancer Institute of New Jersey, New Brunswick, New Jersey, and a Professor at the Institute for Advanced Study in the School of Natural Sciences, Princeton, New Jersey. He was previously the President and CEO of The Rockefeller University in New York. Dr. Levine is one of the world's leading authorities on the molecular basis of cancer, discovering in 1979 the p53 tumor suppressor protein, a molecule that inhibits tumor development. Dr. Levine earned his Ph.D. in Microbiology from the University of Pennsylvania School of Medicine in 1966, and later became a Postdoctoral Fellow at the California Institute of Technology. Dr. Levine is a member of several academic associations, including the American Society for Microbiology, the American Association for the Advancement of Science, the Advisory and Educational Committee of the Association of Medical School Microbiology Chairman from 1979 to 1984, the American Association for Cancer Research, and the American Association of Virology. Among his many awards, Dr. Levine has recently received the 2000 Keio Medical Science Prize, Keio University Medical Science Fund, Japan; the 2001 Alfred Knudson Award in Cancer Genetics from the National Cancer Institute; the 2001 Albany Medical Center Prize in Medicine and Biomedical Research from Albany Medical Center; the 2001 Jill Rose Award from the Breast Cancer Research Foundation; and the 2003 Award for Basic Research from the Surgical Society of Oncologists.

Bill Beers will introduce Dr. Levine.  Dr. Beers is the Chief Academic and Scientific Officer of the MBL. Dr. Beers received an A.B. in Biochemical Sciences from Harvard, completed his doctorate in Biochemistry and Pharmacology at The Rockefeller University, and held a postdoctoral fellowship at the University of Illinois before serving as an Associate and Assistant Professor of Cell Biology at The Rockefeller University from 1973 to 1978. Dr. Beers joined the faculty of New York University in 1978, where he served as a Professor in the Departments of Biology and Cell Biology, as well as Biology Department Chair and  Director of Undergraduate Studies. From 1987 to 2000, Dr. Beers held various positions at The Scripps Research Institute in La Jolla, California. There he oversaw all scientific departments and support services, and acted as a key player in the articulation and implementation of the Institute’s vision and mission. Dr. Beers served as Vice President of Facilities and Research Support at The Rockefeller University from 2000 to 2002. Prior to joining the MBL, Dr. Beers had been Vice President of Operations and a member of the Board of Trustees of The Torrey Pines Institute for Molecular Studies in San Diego. Dr. Beers has conducted research in the area of female reproduction and is the author of numerous publications in leading scientific journals. He has served as a Trustee of several institutions and currently serves on the Boards of SciTekMedia, Inc., the Foundation for Biomedical Research, and the Torrey Pines Institute for Molecular Studies. Dr. Beers has received the Rockefeller Foundation Special Postdoctoral Fellowship in Reproductive Biology, the Public Health Service Research Career Development Award, and the Dean's Distinguished Faculty Award from New York University.