The hormone receptor-positive (HR+) type is the most frequently identified subtype of breast cancer. HR+ breast cancer has a more positive prognosis when compared to other subtypes, such as human epidermal growth factor protein 2-positive disorder and triple-negative disease. The advancement in treatment outcomes for advanced HR+ breast cancer has been considerably elevated due to the discovery of cyclin-dependent kinase 4/6 inhibitors and their combination effects with endocrine therapy. However, despite the considerable effectiveness of tamoxifen, a selective estrogen receptor modulator (SERMs), and aromatase inhibitors (AI), the issue of treatment resistance still presents a significant challenge for HR+ breast cancer. As a result, there is a focus on exploring new therapeutic strategies such as targeted protein degradation and covalent inhibition for targeting ERα. This article discusses the latest progress in treatments like oral selective ER degraders (SERDs), complete estrogen receptor antagonists (CERANs), selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimera (PROTAC) degraders, and combinations of CDK4/6 inhibitors with endocrine therapy. The focus is specifically on those compounds that have transitioned into phases of clinical development.
激素受体阳性（HR+）型是乳腺癌中最常见的亚型。相较于人表皮生长因子蛋白2阳性异常和三阴性等其他亚型，HR+乳腺癌的预后更为乐观。由于细胞周期蛋白依赖性激酶4/6抑制剂的发现及其与内分泌治疗的联合效应，晚期HR+乳腺癌的治疗效果已显著提升。然而，尽管选择性雌激素受体调节剂（SERMs）如他莫昔芬和芳香化酶抑制剂（AI）具有显著疗效，但治疗耐药性问题仍然是HR+乳腺癌面临的重要挑战。因此，当前研究重点转向探索新的治疗策略，如靶向蛋白降解和共价抑制以针对ERα。本文讨论了口服选择性ER降解剂（SERDs）、完全雌激素受体拮抗剂（CERANs）、选择性雌激素受体共价拮抗剂（SERCAs）、蛋白水解靶向嵌合体（PROTAC）降解剂以及CDK4/6抑制剂与内分泌治疗联合应用的最新进展，特别关注已进入临床开发阶段的化合物。
肿瘤(癌症)患者之家