Lewis C. Cantley, PhD
Professor of Cell Biology, Harvard Medical School
Understanding how cellular signals alter breast cancer growth and response to therapy and identifying ways to enhance the effectiveness of targeted cancer therapies.
Dr. Cantley was the first to discover PI3K, a protein controlled by PIK3CA, the most frequently mutated gene in breast cancer. The P13K inhibitor, alpelisib, has been approved for treating metastatic breast cancer but its effectiveness has been limited because tumor cells can activate other growth pathways to counter its effects. Dr. Cantley’s group has focused on the role of the PI3K in breast cancer growth and metastasis. His group has identified proteins that can modify [the function of] PI3K as well as ways to target the protein to block PI3K activity. This finding may help identify new ways to target PI3K to treat metastatic breast cancer. In other studies, Dr. Cantley has focused on developing a novel therapeutic strategy for the treatment of breast cancers with BRCA mutations, which are often particularly aggressive and hard-to-treat. Taken together, Dr. Cantley’s research have the potential to develop novel ways to improve treatment outcomes for metastatic breast cancer patients.
Studies have shown that high doses of two vitamins can generate metabolic toxins specifically in BRCA1-mutant cancer cells: folate generates formaldehyde which can kill BRCA-defective cancer cells; and vitamin C triggers the accumulation of several other toxins. Dr. Cantley showed that folate and vitamin C work together to kill BRCA1- and BRCA2-defective cancer cells by generating reactive oxygen species, which are toxic to the cells. Building on these findings, the team designed preclinical studies to assess the effect of folate alone or in combination with vitamin C.
Dr. Cantley and his team will continue to test the efficacy of folate alone or in combination with vitamin C in laboratory models. One target of interest is a protein responsible for transporting folate into the cell that is commonly overexpressed in breast cancers. The team will examine the role of the folate transporter protein in folate toxicity in BRCA1-defective cells. These studies may provide insight into new treatments for BRCA1-associated breast cancers.
Lewis C. Cantley, PhD, is a professor of cell biology at Harvard Medical School. Prior to this appointment, he was 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 (2012-22). Dr. Cantley is a graduate of West Virginia Wesleyan College, obtained a PhD in biophysical chemistry from Cornell University, completed postdoctoral training at Harvard University, and subsequently taught and conducted research in biochemistry, physiology and cancer biology 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 National Academy of Inventors in 2020, the Institute of Medicine in 2014, the National Academy of Sciences in 2001, and 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.
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