PDF(Pubmed)
Abstract：
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 de novo 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. De novo 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 (INSM1) 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 (TP53) and retinoblastoma 1 (RB1). 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 TP53 and RB1 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.
摘要：
与前列腺癌（PCa）相比，神经内分泌前列腺癌（NEPC）显示出攻击行为，也被称为前列腺腺癌。PCa中的小病灶可能带有遗传交替，这可能在前列腺癌的异质性中出现。NEPC可能从头出现或在雄激素剥夺治疗（ADT）后发展。ADT后出现的NEPC的命名为“治疗出现/诱导NEPC（t-NEPC）”。t-NEPC有望用于去势抵抗前列腺癌（CRPC）和转移性PCa。t-NEPC的特征是雄激素受体（AR）表达低或缺失，AR信号的独立性，并获得神经内分泌表型。t-NEPC是一种侵袭性转移性肿瘤,从PCa发展来响应药物诱导的ADT，对常规治疗反应非常短。t-NEPC发生在10％-17％的CRPC患者中。从头NEPC很少见，占所有PCa的不到2％。从CRPC转分化为t-NEPC的分子机制尚未完全阐明。鞘氨醇激酶1在t-NEPC发育中起重要作用。虽然神经内分泌标志物：突触素，嗜铬粒蛋白A,和胰岛素瘤相关蛋白1（INSM1）在t-NEPC中表达，它们对诊断是非特异性的，预后,和后续治疗。t-NEPC在肿瘤蛋白P53(TP53)和视网膜母细胞瘤1(RB1)中显示富集的基因组改变。有证据表明，t-NEPC可能通过表观遗传进化发展。有基因组，表观遗传,和据报道参与t-NEPC发展的转录改变。发现TP53和RB1的敲除有助于t-NEPC的发展。PCa对免疫疗法有抗药性,目前正在进行针对PCa的免疫治疗试验，CRPC,和t-NEPC。
