Neuroendocrine prostate cancer (NEPC) is a highly aggressive variant of castration-resistant prostate cancer. It is characterized by low or no expression of the androgen receptor (AR), activation of AR-independent signaling, and increased neuroendocrine phenotype. Most of NEPC is induced by treatment of androgen deprivation therapy and androgen receptor pathway inhibitors (ARPIs). Currently, the treatment of NEPC follows the treatment strategy for small-cell lung cancer, lacking effective drugs and specific treatment options. This review summarizes potential novel targets and therapies for NEPC treatment, including epigenetic regulators (zeste homolog 2 inhibitors, lysine-specific demethylase 1 inhibitors), aurora kinase A inhibitors, poly-ADP-ribose polymerase inhibitors, delta-like ligand 3 targeted therapies, a combination of immunotherapies, etc. Other promising targets and future directions are also discussed in this review. These novel targets and therapies may provide new opportunities for the treatment of NEPC.

The treatment of metastatic castration-resistant prostate cancer (mCRPC) remains a huge challenge. Newer radionuclides, such as ²²³ Ra, ¹⁷⁷ Lu, ²²⁵ Ac, etc., have shown efficacy in alleviating cancer-related pain and also in enhancing the prognosis of mCRPC patients. These novel radionuclides have emerged as important weapons in the treatment of mCRPC. This article reviews recent advances and key clinical trials in various radionuclides and their combinations in the application for treating mCRPC. Further directions of this new treatment strategy are also discussed in this review.