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 growth-independent behavior of castration resistant prostate cancer and will test the ability of drugs that target Hedgehog or Gli as a means to suppress this behavior. The work has 3 Aims. Work in the first Aim will determine the specific roles of Smoothened or Gli2 in generating this behavior; work in Aim 2 will characterize the interaction between the AR and Gli2 to identify mechanisms of Gli2 support of AR activity in an androgen- deprived environment; work in Aim 3 will determine the extent to which Gli activity is involved in intratumoral steroidogenesis that supports androgen growth independence of advanced prostate cancer. The ultimate goal of the project is to define the mechanisms by which Hedgehog signaling molecules support aggressive cancer behaviors and to identify treatments that target the specific mechanisms as preclinical testing for potential use in advanced (metastatic) prostate cancer patients.