Dana-Farber Cancer Institute Boston, Massachusetts
Professor of Cancer Biology Harvard Medical School
Gaining a better understanding of cellular signaling and metabolism in cancer cells in order to improve breast cancer treatment.
BRCA1 mutations are common in breast cancer, especially in aggressive and hard-to-treat tumors. While PARP inhibitors have been effective for treating these tumors, resistance often develops. Therefore, new therapeutic strategies are necessary to provide options for patients with BRCA1-mutant breast cancer. Studies have shown that two specific vitamins can generate toxins that affect BRCA1-mutant cells selectively. Dr. Cantley is investigating the mechanism of action of these vitamins to exploit their detrimental effects on these tumors. Using laboratory models, he is assessing the efficacy of combining these vitamins to treat breast cancer and hopes to uncover a novel strategy for treating aggressive BRCA1-mutant tumors.
Studies have shown that high doses of two vitamins can generate metabolic toxins specifically in BRCA1-mutant cancer cells. Using a combination of metabolic and molecular biology tools, Dr. Cantley and his team showed that these two vitamins 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 therapeutic efficacy of combining these two vitamins. In the last year, they developed a regimen for administration of these vitamins and tested it in laboratory models. Their laboratory studies showed the combination to be non-toxic to normal cells providing another reason to combine the two vitamins for cancer therapy. Further, the Cantley team demonstrated that treatment with the vitamin combination prolongs the survival even in models of BRCA1-mutant cells.
In the coming year, Dr. Cantley and his colleagues will continue assessing the efficacy of this novel therapeutic strategy in other laboratory models. They will also dissect the mechanism by which these vitamins interact in breast cancer cells. And they will examine whether the vitamin combination potentiates the efficacy of the standard-of-care PARP inhibitor olaparib (Lynparza®) against BRCA1-mutant tumors. These studies may provide insight into new treatments for BRCA1-associated breast cancers that target both metabolic and genetic vulnerabilities of these cells in order to specifically kill them.
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.
2009
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