选择性雌激素受体降解剂研究进展

Advances in Selective Estrogen Receptor Degraders

雌激素受体阳性乳腺癌是乳腺癌最常见的亚型,内分泌治疗是其主要的治疗手段。为克服内分泌治疗中药物不耐受和耐药等问题,开发选择性雌激素受体降解剂(SERD)成为研究热点。为改善SERD的药动学特性,多个口服SERD的临床研究取得了阳性结果。同时,为提高雌激素受体的降解效率,还利用蛋白水解靶向嵌合体、分子胶降解等靶蛋白降解技术开发新型SERD药物。综述内分泌治疗的现状、口服SERD的开发和临床研究及新型雌激素受体降解技术药物的研发进展,以期为改善乳腺癌患者的预后提供参考。

Estrogen receptor-positive breast cancer is the most common subtype,which is most commonly treated with endocrine therapy.In order to address the issues of drug resistance and intolerance in endocrine therapy,selective estrogen receptor degrader(SERD)has become a hotspot in the research.Several oral SERDs have been developed to improve the pharmacokinetic properties with positive results in several clinical studies.Besides,novel target protein degradation technologies have been adopted to improve the degradation efficiency of estrogen receptor,with new SERDs being developed through protein hydrolysis targeting chimera and molecular gel technologies.This article reviews the status of endocrine therapy and the progress in the development and clinical research of oral SERD and novel protein degradation drugs,in the hope of providing some reference for the improvement of the prognosis of breast cancer patients.