Garvan Institute of Medical Research, Sydney, NSW, Australia.
School of Clinical Medicine, St Vincent's Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
Drug Des Devel Ther. 2022 Sep 2;16:2933-2948. doi: 10.2147/DDDT.S380925. eCollection 2022.
Several endocrine therapies are currently available for the treatment of estrogen receptor (ER) positive breast cancer, but the clinical benefit of these agents is limited by endocrine therapy drug resistance. A common mechanism of endocrine therapy resistance is mutations. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has activity against mutant tumors but requires intramuscular injection and has poor bioavailability that precludes optimal drug dosing. This led to the development of second-generation SERDs which are potent and have improved oral bioavailability and pharmacokinetics. Several of these oral SERDs are now in phase III trials in both the early and advanced ER positive breast cancer settings. This review summarizes the background of oral SERD development, the current status and future perspectives.
目前有几种内分泌疗法可用于治疗雌激素受体 (ER) 阳性乳腺癌，但这些药物的临床获益受到内分泌治疗耐药性的限制。内分泌治疗耐药的一个常见机制是 突变。第一代选择性雌激素受体降解剂 (SERD) 氟维司群对 突变肿瘤有活性，但需要肌肉注射，且生物利用度差，无法进行最佳药物剂量。这导致了第二代 SERD 的开发，它们具有更强的活性，并且改善了口服生物利用度和药代动力学。目前，这些口服 SERD 中的几种正在早期和晚期 ER 阳性乳腺癌环境的 III 期临床试验中进行研究。本文综述了口服 SERD 开发的背景、现状和未来展望。
