The progression of a cancer from the initiating cancer stem cell (CSC) to clinical significance, and ultimately to recurrence after treatment failure, is the culmination of a continuously evolving reciprocal interaction between the CSC and the
Androgen deprivation therapy (ADT) has been the standard-of-care for advanced prostate cancer (CaP) for 60 years, but rarely is curative and has significant side-effects. This project proposes 2 complementary using strengths of ADT. First, transient ADT will expose the inaccessible CaP stem cell to short-term targeted therapy. Second, movement of circulating androgens across the micro-vascular barrier will be blocked by inhibiting endothelial cell-mediated androgen transport, a prostate-specific ADT, to prevent access of circulating adrenal androgens to CaP to minimize systemic collateral side effects.
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