Fei Xin, Xue Jia-Wei, Wu Ji-Zhongrong, Yang Chong-Yi, Wang Ke-Jie, Ma Qi
Health Science Center, Ningbo University, Ningbo, Zhejiang, China.
Department of Urology, The First Hospital of Ninghai, Ningbo, China.
Ther Adv Med Oncol. 2024 Aug 8;16:17588359241269676. doi: 10.1177/17588359241269676. eCollection 2024.
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.
神经内分泌前列腺癌（NEPC）是去势抵抗性前列腺癌的一种高度侵袭性变体。其特征在于雄激素受体（AR）低表达或无表达、AR非依赖性信号激活以及神经内分泌表型增加。大多数NEPC是由雄激素剥夺疗法和雄激素受体通路抑制剂（ARPI）治疗诱导产生的。目前，NEPC的治疗遵循小细胞肺癌的治疗策略，缺乏有效的药物和特定的治疗选择。本综述总结了NEPC治疗的潜在新靶点和疗法，包括表观遗传调节剂（zeste同源物2抑制剂、赖氨酸特异性去甲基化酶1抑制剂）、极光激酶A抑制剂、聚ADP核糖聚合酶抑制剂、Delta样配体3靶向疗法、免疫疗法组合等。本综述还讨论了其他有前景的靶点和未来方向。这些新靶点和疗法可能为NEPC的治疗提供新机会。
