Mechanisms of neuroendocrine differentiation in castration-resistant prostate cancer and advances in the treatment of neuroendocrine prostate cancer

Abstract

Aims: Prostate cancer (PC) is a common male malignancy. Although androgen deprivation therapy (ADT) is standard for advanced PC, many patients develop castration-resistant PC (CRPC), and some progress to neuroendocrine PC (NEPC). This study aims to clarify mechanisms of this transition, especially the role of cancer stem cells (CSCs), and explore therapeutic targets. Methods: A literature review was conducted on genetic alterations, signaling pathways, tumor microenvironment, and CSC biology related to CRPC and NEPC progression. Findings: Evidence shows that lineage plasticity, alternative signaling activation, and CSC expansion drive CRPC and NEPC development. CSCs promote heterogeneity, resistance, and metastasis, while current treatments remain largely ineffective for NEPC. Conclusions: Understanding mechanisms of PC progression is crucial for new interventions. Targeting CSC-related pathways may help prevent resistance and improve outcomes in advanced prostate cancer.