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Lewis C. Cantley, PhD
Director, Sandra and Edward Meyer Cancer Center,
Ronald P. Stanton Clinical Cancer Program at New York-Presbyterian
Margaret and Herman Sokol Professor in Oncology Research
Professor of Cancer Biology in Medicine
Weill Cornell Medical College
New York, New York
- Studying the processes that regulate normal cell growth to understand the defects that lead to cancer.
- Laboratory and clinical studies are planned to understand the effects of targeted therapy on metabolism to identify strategies to prevent resistance.
- These studies will provide valuable information to improve response to targeted therapies for patients with breast and other cancers.
The concept of “targeted” cancer therapy is to target the source driving tumor growth with the idea that shutting down its addiction will cause the tumor to die. Unfortunately, the success of many “targeted” therapies is hampered by the tumor cells’ ability to activate other means of growth, rendering the therapy ineffective. Dr. Cantley is conducting studies to improve the effectiveness of one type of targeted therapy called PI3K inhibitors. His group is testing a novel combination approach to prevent resistance to these drugs.
Full Research Summary
Two of the most frequently mutated genes in breast cancer, PIK3CA and PTEN, encode enzymes that mediate cellular responses to insulin. Although many PI3K inhibitors have entered clinical trials for treating breast cancers, their impact has been limited.
One mechanism of resistance to PI3K inhibitors in tumor cells is the activation of alternative pathways, making the cells less dependent on the drug target for survival. Blocking the PI3K pathway has another effect due to its regulation of insulin; It causes a dramatic increase in circulating insulin, as is seen with acute insulin resistance.
In an article published in the journal Nature, Dr. Cantley’s team showed that this dramatic elevation in serum insulin reactivates PI3K in tumors, overriding the effects of the PI3K inhibitor and reducing the effectiveness of the drug. He has also shown that this can be circumvented with a low carbohydrate diet increasing the efficacy of PI3K inhibitors in laboratory models of cancer.
In the coming year, he is planning a clinical trial to evaluate a PI3K inhibitor called copanlisib, which was recently FDA-approved for treatment of lymphoma, in combination with a low carbohydrate diet in multiple cancers, including breast cancer.
In addition, his group is continuing studies on the effect of different diets on tumor growth and immune cells in the tumor microenvironment in response in PI3K inhibitors.
These studies could provide a rationale for combining immunotherapy drugs with PI3K inhibitors and dietary intervention for treatment of breast cancers.
Lewis C. Cantley, PhD, is the Margaret and Herman Sokol Professor and Meyer Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medical College/Ronald P. Stanton Clinical Cancer Program at New York Presbyterian Hospital. Dr. Cantley grew up in West Virginia and graduated from West Virginia Wesleyan College in 1971. He obtained a PhD in biophysical chemistry from Cornell University in 1975 and did postdoctoral training at Harvard University. Prior to taking the position at Weill Cornell, he taught and did research in biochemistry, physiology and cancer biology in Boston, most recently at Beth Israel Deaconess Medical Center and Harvard Medical School. His laboratory discovered the PI 3-Kinase pathway that plays a critical role in insulin signaling and in cancers.
Dr. Cantley was elected to the Institute of Medicine in 2014, to the National Academy of Sciences in 2001 and to the American Academy of Arts and Sciences in 1999. Among his other awards are the ASBMB Avanti Award for Lipid Research in 1998, the Heinrich Wieland Preis for Lipid Research in 2000, the Caledonian Prize from the Royal Society of Edinburgh in 2002, the 2005 Pezcoller Foundation–AACR International Award for Cancer Research, the 2009 Rolf Luft Award for Diabetes and Endocrinology Research from the Karolinska Institute, Stockholm, the 2011 Pasrow Prize for Cancer Research, the 2013 Breakthrough in Life Sciences Prize and the 2013 Jacobaeus Prize for Diabetes Research from the Karolinska Institute and the 2015 AACR Princess Takamatsu Memorial Lectureship.