Chemical Suppression of the Reactivated Androgen Signaling Pathway in Androgen-Independent Prostate Cancer.

摘要

The project studies the role of Hedgehog/Gli Signaling in generating the androgen-independent growth phenotype of castration resistant prostate cancer and will test the ability of drugs that target Hedgehog/Gli as a means to suppress the androgen independent growth behavior associated with castration resistant prostate cancer. The work has 3 Aims and work will determine the specific roles for Hedgehog signaling molecules, Smo and Gli in androgen independent growth behavior; work in Aim 2 will characterize the interaction between the androgen receptor (AR) and Gli2 to identify mechanisms of Gli support of AR activity in an androgen-free microenvironment; work in Aim 3 will determine the extent to which Gli activity is involved in intratumoral steroidogenesis that is believed to drive resistance to castration- and other hormonal therapies. The collective goal of this project is to understand the basis for Hedgehog/Gli support of castration-resistant prostate cancer and to identify the appropriate small chemicals that target the signaling network as a prelude to validating new, more effective treatments for castration-resistant prostate cancer.