University of Cambridge > > Seminars at the Department of Biochemistry > Alkis Seraphim Lecture 2018 - PI 3-Kinase and Cancer Metabolism

Alkis Seraphim Lecture 2018 - PI 3-Kinase and Cancer Metabolism

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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 be activated by insulin. Mosaic mutations in PIK3CA during development are the cause of a variety of localized overgrowth syndromes called PROS , in which glucose uptake and anabolic metabolism is dramatically enhanced. The observation that PIK3CA mutations enhance responses to insulin raises the possibility that elevated levels of serum insulin could drive the growth of tumors that express the insulin receptor. PI3K inhibitors that target PIK3CA are in clinical trials and have the expected physiological effect of raising serum glucose and insulin levels. The elevated serum insulin has the potential to reactivate PI3K in the tumor, potentially explaining why PI3K inhibitors are not as effective as expected in treating cancers with PIK3CA mutations. Data will be presented showing that dietary and pharmaceutical interventions that limit elevation of serum insulin improve responses to PI3K inhibitors in mouse models of cancer. The role of PI3K in driving anabolic metabolism will also be discussed.

This talk is part of the Seminars at the Department of Biochemistry series.

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