Non-androgen Signaling Pathways in Castration-Resistant Prostate Cancer

Abstract

Prostate cancer (PCa), while initially androgen-sensitive, the lethal form of the disease inevitably progresses to hormone refractory or castration-resistant state and accounts for vast majority of mortality among PCa patients. During the transition from the hormone naive disease into CRPC, the progression of PCa cells can be driven by alternative (non-androgen) signaling pathways. Upregulation of ligands, receptors and intracellular signaling molecules along with activating mutations of proto-oncogenes and/or suppression of tumor suppressor genes are the major causes of the deregulation of these alternative pathways. In addition, loss of negative feedback mechanism of the signal cascades further amplifies the effects of the pathways and thus contributing to the emergence of CRPC. This chapter covers studies investigating the potential involvement of non-androgen signaling pathways in PCa and the current strategies employed in PCa cell lines, animal models and clinical trials for controlling these aberrant signaling pathways. The understanding of non-androgen signaling pathway target(s) in CRPC could provide novel biomarkers and newer strategies in management of metastatic PCa.