Prostate Cancer Development, Progression, and Therapy

Abstract

Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer death in men worldwide. Understanding the signaling pathways and molecular mechanisms that drive PCa development and progression is essential for developing new treatments. In this review, we provide an overview of the history and advancements in PCa's detection, diagnosis, surgical intervention, hormonal therapy, chemotherapy, and radiotherapy. We reviewed genetic alterations and their roles in PCa tumorigenesis. We also summarized the molecular mechanisms that drive the transition from castration-sensitive PCa (CSPC) to castration-resistant PCa (CRPC), along with factors that promote lineage plasticity from AR-positive CRPC to neuroendocrine PCa (NEPC) and double-negative PCa (DNPC). We further examined recent advances in immunotherapies, including CAR-T, PARP inhibitors, proteolysis-targeting chimeras (PROTACs), and antibody-drug conjugates (ADCs). Finally, we provide perspectives regarding the opportunities and challenges in detection, diagnosis, and therapy of PCa and future directions for the investigation of molecular mechanisms of prostate cancer development, progression, and therapy resistance. This review provides a framework that connects historical milestones with current molecular insights and offers a roadmap for future precision oncology strategies in prostate cancer.

Keywords

androgen receptor / castration resistance / immunotherapy / lineage plasticity / prostate cancer / targeted therapy

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