Abstract: 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 ESR1 mutations. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has activity against ESR1 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.

Keywords: selective estrogen receptor degraders, breast cancer, estrogen receptor


中文翻译：

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乳腺癌中的口服选择性雌激素受体降解剂 (SERD)：进展、挑战和现状

摘要：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，但这些药物的临床益处受到内分泌疗法耐药性的限制。内分泌治疗耐药的常见机制是ESR1突变。第一代选择性雌激素受体降解剂（SERD）氟维司群对ESR1具有活性突变肿瘤，但需要肌肉内注射，并且生物利用度差，无法进行最佳药物给药。这导致了第二代SERD的开发，这些SERD是有效的并且具有改善的口服生物利用度和药代动力学。这些口服 SERD 中的一些现在正处于早期和晚期 ER 阳性乳腺癌环境中的 III 期试验中。本综述总结了口腔SERD发展的背景、现状和未来展望。

关键词：选择性雌激素受体降解剂，乳腺癌，雌激素受体