Unraveling molecular characteristics and tumor microenvironment dynamics of neuroendocrine prostate cancer

Prostate cancer (PCa) is the most prevalent malignancy and the second leading cause of cancer-related deaths among men. While adenocarcinoma of the prostate (adeno-PCa) is well-characterized, neuroendocrine prostate cancer (NEPC) remains poorly understood. Generally, NEPC is a rare but highly aggressive histological variant, however its limited patho-physiological understanding leads to insufficient treatment options associated with low survival rates for NEPC patients. Current treatments for NEPC, including platinum-based therapies, offer some efficacy, but there is a significant need for more targeted approaches. This review summarizes the molecular characteristics of NEPC in contrast to adeno-PCa, providing a comprehensive comparison. A significant portion of the discussion is dedicated to the tumor microenvironment (TME), which has recently been identified as a key factor in tumor progression. The TME includes various cells, signaling molecules, and the extracellular matrix surrounding the tumor, all of which play critical roles in cancer development and response to treatment. Understanding the TME's influence on NEPC could uncover new avenues for innovative treatment strategies, potentially improving outcomes for patients with this challenging variant of PCa.