Chemical Suppression of the Reactivated Androgen Signaling Pathway in Androgen-Independent Prostate Cancer
Annual rept. 1 Jul 2010-30 Jun 2011
ORDWAY RESEARCH INST ALBANY NY
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The project studies the relationship between Hedgehog Signaling and hyperactive androgen signaling in androgen independent prostate cancer and tests the idea that Hedgehog inhibitors can block hyperactive androgen signaling leading to suppression of castration resistant tumor growth. Progress during this first annual period has established a relationship between the expression andor activity of Hedgehog signaling proteins Smoothened, Gli1 and Gli2 and increased androgen signaling and androgen independent AI growth of prostate cancer cells. Other work has linked Hedgehog signaling activity in prostate cells to the biosynthesis of testosterone. These data supports the idea that Hedgehog activity in an androgen deprived tumor both sensitizes the tumor cell to low levels of androgen and increases the local production of androgen in the tumor microenvironment and both have the potential to increase tumor growth in androgen deprived conditions. The outcomes are consistent with the idea that Hedgehog inhibitory drugs have a significant potential for treatment of advanced prostate cancer.
- Anatomy and Physiology
- Medicine and Medical Research