Terence Friedlander

About Terence Friedlander

Investigation of genomic mechanisms of androgen biosynthesis inhibitor resistance in castration resistant prostate cancer

In most cases the first line of therapy for patients with prostate cancer is Androgen Deprivation Therapy (ADT). ADT aims to deplete the levels of androgens, the male hormones that bind to their receptor (Androgen Receptor-AR) and drive prostate cancer progression. One of the medications used for ADT is the recently FDA-approved Abiraterone (Zytiga) which targets the biosynthesis of androgens in the adrenal glands and more importantly, in the tumor itself. Though patients respond well to Abiraterone and other ADT medications, almost all develop resistance to this therapy and their cancers progress. This stage of treatment resistance is termed castration resistant prostate cancer (CRPC). CRPC is hypothesized to develop due to either 1) the increased production of androgens by the tumor itself, or 2) mutations in the AR that make it independent of the presence/absence of androgens.

Dr. Terence Friedlander proposes to investigate the specific genetic changes in prostate cancer cells that occur during the development and progression of castration resistance. He will determine whether CRPC is mediated by the upregulation of androgen synthesis by the tumors or whether castration resistance is mediated by androgen-independent AR activity. During the course of these investigations, Dr. Friedlander will conduct two separate clinical trials: one that evaluates the effectiveness of using an increased-dose of abiraterone in men who have developed resistance to standard-dose abiraterone, and a second trial that evaluates the effect of treating men with abiraterone resistance, with a new hormonal medication called ARN-509. Dr. Friedlander will collect metastatic tumor biopsies and circulating tumor cells from these patients to evaluate the precise mechanisms underlying abiraterone resistance. A better understanding of the mechanisms that cause CRPC development will allow clinicians to optimize and sequence the new therapies available for the treatment of CRPC.