Grant: Project Grant

Prostate cancer arises as an androgen driven disease and androgen deprivation therapies (ADTs) are the mainstay of systemic therapies for patients with advanced disease. Although ADTs offers remission, this is temporary, as the cancer resurfaces as castration-resistant PC (CRPC) and in a small percentage of cases, cells trans-differentiate into neuro-endocrine PC (NEPC). While there is a biologic continuum with prostate adenocarcinoma evolving from a hormone naïve state (HNPC) to CRPC to NEPC, we found the enzyme telomerase is overexpressed all these states. By upregulating telomerase, these prostate cancer cells overcome the finite replicative life span and gain potential for unlimited growth. In fact, targeting the enzyme telomerase with inhibitors is pursued as a potential avenue for treating cancer patients. Unfortunately, despite several efforts, such inhibitors were so far ineffective in clinical trials. Here we propose to identify and validate alternative druggable targets, that are essential for the survival of telomerase overexpressing HNPC, CRPC and NEPC. This way, normal cells that do not express telomerase remain unaffected. The targets identified and validated in this study can eventually lead to effective prostate cancer therapies.