去势抵抗性神经内分泌前列腺癌发病中的基因变化及治疗研究进展

Progression of treatment and gene alterations of castration-resistant neuroendocrine prostate cancer

前列腺癌是男性健康的主要杀手。临床研究表明,随着抗雄治疗的普遍应用,前列腺癌(prostate cancer,PCa)患者生存期中大部分时间均处于去势抵抗阶段。去势抵抗性神经内分泌前列腺癌(castration-resistant neuroendocrine PCa,CRPC-NE)是去势抵抗性前列腺癌(castration-resistant PCa,CRPC)的少见亚型及难治亚型,该病致死率高,治疗难度极大。科研人员为提高CRPC-NE的生存率对其机制进行了探索,发现N-MYC、RB1/TP53、TMPRSS2-ERG等一系列基因的改变与CRPC-NE的演进息息相关,并认为SPDEF的显著超甲基化可促进CRPC-NE的进展。研究人员尝试依据现有的分子生物学变化制定治疗方案,研发出了Alisertib等新型靶向药物,并尝试通过CD46等免疫靶点及IFN-β1a等细胞因子对CRPC-NE进行精准治疗,以期提高患者的生存率与生存时间。

Prostate cancer is the leading cause of cancer-related death rate among men.The results of clinical trials demonstrate that metastatic castration-resistant PCa makes up most of survival time.CRPC-NE is the rare subset as well as the refractory subset of CRPC,which is short for Castration-resistant neuroendocrine PCa.CRPC-NE has high fatality rate and difficult to cure.Researchers explore the alterations of tumor cells to rise the survival rate of CRPC-NE and figure out some genes,like N-MYC,RB1/TP53,TMPRSS2-ERG and SPDEF,leading to the evolution of CRPC-NE.Institutions struggle to find out the effective treatment according to the existing findings.Finally,researchers find targeted drugs including Aliserti and try to use CD46 as well as IFN-β1a to meet requirement of precise treatment.