去势抵抗性前列腺癌新型内分泌药物治疗次序的研究进展

Progress on resistance to new endocrine therapy in castration-resistant prostate cancer

前列腺癌(prostate cancer,PCa)是欧美男性中常见的肿瘤,近年来其在中国的发病率成上升趋势。去势抵抗前列腺癌(castration-resistant prostate cancer,CRPC)阶段是前列腺癌治疗的重点和难点,PCa进入CRPC后雄激素受体(androgen receptor,AR)信号轴对于肿瘤的生存和进展依然发挥重要作用,以AR信号轴为作用靶点是新型内分泌治疗药物的特点,阿比特龙和恩杂鲁胺是其中的代表,二者可有效抑制AR信号轴的活性,延长患者的生存期。虽然新型内分泌治疗药物对CRPC安全有效,但随之而来的耐药问题严重影响了临床疗效。本文将综述近年来新型内分泌治疗药物耐药机制的研究进展,为克服耐药问题和开发新药提供借鉴。

The incidence of prostate cancer in China has a rising trend recently. The majority of prostate cancer patients have been in advanced stage at the first diagnosis. Although the endocrine therapy may make prostate cancer under control and improvement in a certain period of time, but almost patients will finally develop to metastatic castration-resistant prostate cancer（m CRPC） with poor prognosis after 18-24 months of remission period. Because m CRPC is difficult to cure, it is urgent to optimize the treatment strategy for improving efficacy. The current evidence shows that the new endocrine drugs such as abiraterone and enzalutamide combined with docetaxel chemotherapy can provide survival benefit for the patients with m CRPC, but there is still a controversy about the optimal using order of these agents. The article reviews the clinical trials on the treatment sequencing of noval endocrine agents in docetaxel-experienced and docetaxel-naive patients with m CRPC in order to provide the basisfor the correct selection of treatment strategies, and thus to prolong the overall survival and improve the quality of life of the patients.