The Quartet of Core Oncogenic Drivers in Neuroendocrine Prostate Cancer: Multi-Omics Dataset Integration to Forge a Translational Link Between Biology and Precision Therapy

Prostate cancer (PC) is the most common cancer among American men and the second leading cause of cancer-related deaths. For advanced or metastatic PC, anti-androgen therapies, including androgen deprivation therapy (ADT), are considered standard treatment options. However, these therapies often result in the development of castration-resistant prostate cancer (CRPC) or neuroendocrine prostate cancer (NEPC), both of which present significant treatment challenge. The molecular mechanisms driving the progression from androgen - sensitive PC to castration-resistant and neuroendocrine phenotypes are still being actively investigated. This review aims to comprehensively evaluate the cellular and molecular mechanisms underlying the development of NEPC. Specifically, it will focus on the roles of cancer stem cells (CSCs), epithelial - mesenchymal transition (EMT), and autophagy in the pathogenesis and progression of NEPC. Furthermore, the review will explore the potential of targeting these processes for therapeutic intervention in advanced P. This review will integrate current findings from clinical trials, pre-clinical models, and molecular research to clarify the promising approaches for improving treatment outcomes for patients with advanced PC.