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Upcoming Event

PI 3-Kinase: Linking Obesity, Insulin Resistance and Cancer

The Philip Levine Memorial Lecture

Event Details

Friday Lecture Series
Lewis Cantley, Ph.D., Meyer Director of the Sandra and Edward Meyer Cancer Center, professor of cancer biology in medicine, Weill Cornell Medical College and New-York-Presbyterian

Phosphoinositide 3-Kinase (PI3K) is activated by insulin and other growth factors to mediate cell growth. The PI3K enzyme encoded by the PIK3CA gene is one of the most frequently mutated oncogenes in human cancer. This same enzyme mediates insulin responses in liver, muscle, fat and other tissues. The most common mutations in this gene enhance the ability of PI3K to bind to the insulin receptor substrates, IRS1 and IRS2 and thereby enhance the ability of PI3K to be activated by insulin and IGF1. This observation raises the possibility that elevated levels of serum insulin could enhance the growth of tumors that express the insulin receptor, especially when the tumor expresses a mutant form of PIK3CA. Consistent with this idea, retrospective studies have shown that cancers that correlate with obesity and insulin resistance (conditions where serum insulin levels are high), such as endometrial, breast and colorectal cancers, frequently have activating mutations in PIK3CA. These observations suggest a model in which tumors with mutations in PIK3CA are highly sensitized to insulin-dependent growth and that the elevated serum insulin levels in individuals with insulin resistance in liver, muscle and fat promotes anabolic metabolism in the tumor. Several drugs that inhibit the PI3K encoded by PIK3CA are in phase 3 approval trials for breast cancer and these drugs, as expected, cause acute elevation in serum glucose due to inhibition of insulin signaling in liver, muscle and fat.  This glucose elevation leads to a dramatic elevation in serum insulin, which ultimately brings serum glucose back to normal levels, despite continued high levels of PI3K inhibitor in the serum.  The model discussed above raises the possibility that the elevation in serum insulin may compromise the effectiveness of PI3K inhibitors in killing tumor cells.  Data will be presented showing that dietary interventions that limit elevation of serum insulin improve responses to PI3K inhibitors in mouse models of cancer. 

Lewis Cantley, Ph.D., has made significant advances in cancer research stemming from his discovery of the signaling pathway phosphoinositide 3-kinase (PI3K) in 1984. The author of more than 400 original papers, 50 book chapters and review articles, Dr. Cantley is a fellow of the American Academy of Arts and Sciences and a member of the National Academy of Science, the Institute of Medicine of the National Academies, and the European life sciences academy EMBO. He graduated summa cum laude with a B.S. in chemistry from West Virginia Wesleyan College (1971) and obtained a Ph.D. in biophysical chemistry from Cornell University (1975). He conducted postdoctoral research at Harvard University, where he was appointed assistant professor of biochemistry and molecular biology in 1978. He became a professor of physiology at Tufts University in 1985, but returned to Harvard Medical School as professor of cell biology in 1992. He became chief of Harvard’s new Division of Signal Transduction, and a founding member of its Department of Systems Biology in 2002. In 2007, he was appointed director of the Beth Israel Deaconess Cancer Center. He joined Weill Cornell Medicine as the Meyer Director of the Sandra and Edward Meyer Cancer Center in 2012. Among his accolades are the ASBMB Avanti Award for Lipid Research (1998); the Heinrich Wieland Preis for Lipid Research (2000); the Caledonian Prize from the Royal Society of Edinburgh (2002); the Pezcoller Foundation–AACR International Award for Cancer Research (2005); the Rolf Luft Award for Diabetes and Endocrinology Research from the Karolinska Institute, Stockholm (2009); the Pasarow Prize for Cancer Research (2011); the Breakthrough in Life Sciences Prize (2013); the Jacobaeus Prize for Diabetes Research from the Karolinska Institute (2013); the AACR Princess Takamatsu Memorial Lectureship (2015); the Ross Prize in Molecular Medicine (2015); the Canada Gairdner International Award (2015); the AACI Distinguished Scientist Award (2015); the Hope Funds Award of Excellence in Basic Science (2016); the Wolf Prize (2016); and the NCI Outstanding Investigator Award (2016).

Justin Sloboda
(212) 327-7785
Open to
Titia de Lange, Ph.D.
Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge
Justin Sloboda
(212) 327-7785

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