Promising therapy for neuroendocrine prostate cancer: current status and future directions

• Published in: Therapeutic advances in medical oncology 2024-01, Vol.16, p.17588359241269676
• Main Authors: Fei, Xin, Xue, Jia-Wei, Wu, Ji-zhongrong, Yang, Chong-Yi, Wang, Ke-Jie, Ma, Qi
• Format: Article
• Language: English
• Subjects: Androgen receptors; Aurora kinase; Castration; Epigenetics; Immunotherapy; Phenotypes; Prostate cancer; Small cell lung carcinoma
• ISSN: 1758-8359; 1758-8340; 1758-8359
• DOI: 10.1177/17588359241269676

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. Plain language summary This review summarizes potential novel targets and therapies for NEPC treatment, including epigenetic regulators (EZH2 inhibitors, LSD-1 inhibitors), AURKA inhibitors, PARP inhibitors, and DLL3 targeted therapies, and combination of immunotherapies, etc. These novel targets and therapies may provide new opportunities in the treatment of NEPC.