Wishahi Mohamed
Department of Urology, Theodor Bilharz Research Institute, Cairo 12411, Egypt.
World J Clin Cases. 2024 May 6;12(13):2143-2146. doi: 10.12998/wjcc.v12.i13.2143.
Neuroendocrine prostate cancer (NEPC) shows an aggressive behavior compared to prostate cancer (PCa), also known as prostate adenocarcinoma. Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer. NEPC may arise or develop following androgen deprivation therapy (ADT). NEPC that arise following ADT has the nomenclature "treatment-emerging/induced NEPC (t-NEPC)". t-NEPC would be anticipated in castration resistant prostate cancer (CRPC) and metastatic PCa. t-NEPC is characterized by low or absent androgen receptor (AR) expression, independence of AR signaling, and gain of neuroendocrine phenotype. t-NEPC is an aggressive metastatic tumor, develops from PCa in response to drug induced ADT, and shows very short response to conventional therapy. t-NEPC occurs in 10%-17% of patients with CRPC. NEPC is rare and is accounting for less than 2% of all PCa. The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated. Sphingosine kinase 1 plays a significant role in t-NEPC development. Although neuroendocrine markers: Synaptophysin, chromogranin A, and insulinoma associated protein 1 () are expressed in t-NEPC, they are non-specific for diagnosis, prognosis, and follow-up of therapy. t-NEPC shows enriched genomic alteration in tumor protein P53 () and retinoblastoma 1 (). There are evidences suggest that t-NEPC might develop through epigenetic evolution. There are genomic, epigenetic, and transcriptional alterations that are reported to be involved in development of t-NEPC. Knock-outs of and were found to contribute in development of t-NEPC. PCa is resistant to immunotherapy, and at present there are running trials to approach immunotherapy for PCa, CRPC, and t-NEPC.
神经内分泌前列腺癌（NEPC）与前列腺癌（PCa，也称为前列腺腺癌）相比，具有侵袭性。PCa中的微小病灶可能存在基因改变，这种改变可出现在前列腺癌的异质性中。NEPC可能在雄激素剥夺治疗（ADT）后出现或发展。ADT后出现的NEPC命名为“治疗后出现/诱导性NEPC（t-NEPC）”。t-NEPC预计会出现在去势抵抗性前列腺癌（CRPC）和转移性PCa中。t-NEPC的特征是雄激素受体（AR）表达低或缺失、AR信号通路独立以及神经内分泌表型获得。t-NEPC是一种侵袭性转移性肿瘤，由PCa对药物诱导的ADT产生反应而发展而来，对传统治疗反应非常短暂。t-NEPC发生在10%-17%的CRPC患者中。NEPC很少见，占所有PCa的比例不到2%。CRPC向t-NEPC转分化的分子机制尚未完全阐明。鞘氨醇激酶1在t-NEPC的发展中起重要作用。尽管神经内分泌标志物：突触素、嗜铬粒蛋白A和胰岛瘤相关蛋白1（）在t-NEPC中表达，但它们对诊断、预后和治疗随访并不特异。t-NEPC在肿瘤蛋白P53（）和视网膜母细胞瘤1（）中显示出丰富的基因组改变。有证据表明t-NEPC可能通过表观遗传进化发展而来。据报道，基因组、表观遗传和转录改变参与了t-NEPC的发展。发现敲除和有助于t-NEPC的发展。PCa对免疫疗法有抗性，目前正在进行针对PCa、CRPC和t-NEPC的免疫疗法试验。
