去势抵抗性前列腺癌新型内分泌治疗耐药机制研究进展

前列腺癌是男性泌尿生殖系统最常见的恶性肿瘤之一,雄激素在其发生发展中都扮演着重要角色。经去势治疗(ADT)后绝大多数前列腺癌都会进展成为去势抵抗性前列腺癌(CRPC)。肾上腺来源的雄激素和(或)雄激素受体(AR)的改变(包括AR基因扩增)驱动了瘤内雄激素的合成,进而重新雄激素轴信号通路。目前,阿比特龙、恩扎鲁胺等抗雄激素治疗药物都是CRPC患者的一线治疗用药。但是,治疗一段时间后患者仍然会出现耐药和疾病进展。因此,明确CRPC患者抗雄激素治疗耐药机制可以为克服CRPC治疗耐药和改善CRPC患者的预后提供契机。

Mechanisms of drug resistance in endocrinotherapy for castration-resistant prostate cancer

Androgen plays a significant role in the development and progression of prostate cancer(PCa),one of the commonest malignancies in the male urogenital system.Castration-resistant PCa(CRPC)is the end-result of the majority of prostate cancer cases treated by androgen deprivation therapy(ADT).Furthermore,the androgen axis is reactivated due to adaptive intratumoral androgen biosynthesis,which can be driven by adrenal androgens and/or by changes in the androgen receptor(AR)including AR gene amplification.At present,drugs targeting the androgen axis,such as abiraterone and enzalutamide,et al,are used for the first-line therapy for CRPC.Nevertheless,drug resistance and disease progression occur during the treatment of CRPC by anti-androgen therapy.Therefore,an insight into the mechanisms of drug resistance in anti-androgen therapy for CRPC may help surmount the drug reistance and improve the prognosis of the malignancy.