Abstract
Data regarding the molecular response of prostate cancer to hormone therapy continue to emerge, identifying a complex network of autocrine and paracrine signaling events mediating the tumor response to androgen suppression. Emerging data provide insight into cellular pathways important in the apoptotic response to therapy, including the transforming growth factor-beta, insulin-like growth factor-1, and vascular endothelial growth factor signaling axes. They also reveal mechanisms of direct antitumor cytotoxicity mediated by various hormonal agents and highlight the importance of developing antiandrogens capable of irreversibly inhibiting the androgen receptor. Accumulated data emphasize the presence of residual androgens and persistent activation of androgen receptor signaling in advanced prostate tumors despite castration. These factors suggest that a multitargeted treatment approach designed to ablate all contributions to the androgen receptor signaling axis within the prostate tumor microenvironment will be required in order for hormonal therapy to achieve optimal antitumor efficacy.