Fox Chase Researcher Receives Grant to Study Role of Cholesterol in Resistance to Prostate Cancer Treatment
Posted: Monday, March 2, 2020
On February 25, Vladimir Kolenko, MD, PhD, researcher at Fox Chase Cancer Center, obtained a 2-year $200,000 grant from the National Cancer Institute. Dr. Kolenko and colleagues will investigate the role of cholesterol in resistance to androgen receptor inhibitors in the treatment of prostate cancer. Using genetic and pharmacologic methods, they plan to improve the efficacy of the androgen receptor inhibitor enzalutamide by targeting cholesterol homeostasis.
Enzalutamide is a U.S. Food and Drug Administration–approved second-generation androgen receptor inhibitor for the treatment of both nonmetastatic and metastatic castration-resistant prostate cancer. “These are drugs that are most commonly used to treat metastatic prostate cancer, but eventually tumors develop resistance. Partially, it can be because cholesterol—either [low-density lipoprotein] cholesterol or [high-density lipoprotein] cholesterol, it doesn’t matter which one—can activate prosurvival signaling pathways in prostate cancer cells that can simply bypass the therapeutic effect of antiandrogens,” Dr. Kolenko stated in a Fox Chase press release.
The goal of the study is to re-emphasize sensitivity of prostate cancer cells to androgen receptor inhibitors. “We propose a novel conceptual model that, in addition to serving as a precursor for androgen synthesis, lipoprotein-derived cholesterol may promote development of castration-resistant phenotype in prostate cancer cells via androgen-independent activation of Akt/mTOR signaling.”
