转移性前列腺癌的精准治疗前沿进展

Research progress in precision medicine of metastatic prostate cancer

前列腺癌(PCa)的全球发病率在男性恶性肿瘤中位居第二位,是导致男性死亡的原因之一。局限性PCa患者能够接受根治性手术或者根治性放疗治疗,预后较好。转移性前列腺癌患者失去接受根治性治疗的机会,基于雄激素剥夺疗法(ADT)的去势治疗是转移性前列腺癌患者的治疗基石。但部分患者在疾病缓解的18~24个月后会出现治疗耐药、疾病进展,发展为去势抵抗性前列腺癌(CRPC),最终死亡。随着对PCa研究的深入、基因测序等技术的发展,针对转移性前列腺癌患者的精准治疗成为了目前的研究热点及治疗突破点。包括:针对DNA损伤修复通路的PARP抑制剂、针对PI3K/AKT通路的AKT抑制剂、针对Wnt通路的抑制剂、AR通路的新型雄激素受体拮抗剂以及基于TP53、RB1、CDK4、CCND1等分子的个体化新型药物不断问世。本文主要针对转移性前列腺癌的前沿精准治疗研究进行综述,为新药的开发及转移性前列腺癌的治疗提供信息。

Prostate cancer is one of the most prevalent form of cancers and one of the major causes of mortality for men worldwide.Non-metastatic prostate cancer can receive radical prostatectomy or radical radiotherapy.Androgen deprivation therapy is the cornerstone of the treatment for patients with metastatic prostate cancer.However,some patients showed the potential to develop into castration-resistant prostate cancer because of the progression of disease.For those men who developed metastatic disease,genomic sequencing is now more routinely applied to help guiding the choice of precise medicine,including the selection of PARP inhibitor,AKT inhibitor orandrogen receptor pathway inhibitor.This review provides an up-to-date summary of precision medicine for the management of metastatic prostate cancer.