A comprehensive mechanistic basis of prostate cancer advancement & its personalized implementation-bridging the gap: present state and future prospect

Abstract

Despite significant achievements in prostate cancer mechanistic understanding and its targeted therapies, currently there exists several major challenges that mainly arises during the therapy of advanced prostate cancer. Present prostate cancer precision medicine strategy principally suffers from several practical concerns, particularly in point of therapeutic resistance, tumor heterogeneity, complex clinical & pathological behavior and an extensive genomic perturbation landscape. Prostate Cancer Systems-Medicine Initiative is a global trans-disciplinary movement taken from corresponding scientific domains to critically determine the nature of this major existing challenges and its corresponding most possible solutions by systematically accumulating the present existing knowledge. Basically, it explains the importance of broad spectrum cancer hallmark based integrative approaches for development of combination therapy associated strategic measures for metastatic castration resistant prostate cancer. The major findings of this initiative can be summarized by identification of 136 therapeutic resistance mediators, 103 prostate cancer driver oncogenes and 8 progression pathways along with 5 terrain factors which centrally drives the basic events in prostate cancer pathogenesis, its further metastatic propagation and ultimate therapeutic resistance. In addition, it also attempts to summarize the critical features and basic challenging aspects of current therapeutic options.

Keywords

• precision medicine
• therapy resistance
• cancer hallmarks
• terrain factors
• castration resistant prostate cancer (crpc)
• bone metastasis
• androgen receptor (ar)