Bian Li, Xu Feng-Rui, Jiang Ze-Fei
Department of Breast Oncology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China.
Chin Med J (Engl). 2020 Oct 5;133(19):2338-2345. doi: 10.1097/CM9.0000000000000923.
Increasing numbers of targeted drugs are used in hormone receptor (HR)-positive metastatic breast cancer (MBC) to overcome or delay resistance to endocrine therapy. This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC. From the "AI (aromatase inhibitor) era" represented by aromatase inhibitors, we have gradually entered the "post-AI era" represented by fulvestrant. Under the guidance of research on the molecular mechanism of endocrine therapy resistance, the "combination of endocrine therapy and targeted therapy" era is approaching. The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors, histone deacetylase inhibitors, and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway, providing new strategies for HR-positive MBC. Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.
越来越多的靶向药物被用于激素受体(HR)阳性转移性乳腺癌(MBC),以克服或延缓对内分泌治疗的耐药性。本研究将系统回顾内分泌治疗联合靶向治疗在HR阳性MBC治疗中取得的进展。从以芳香化酶抑制剂为代表的“AI(芳香化酶抑制剂)时代”,我们已逐渐步入以氟维司群为代表的“后AI时代”。在内分泌治疗耐药分子机制研究的指引下,“内分泌治疗与靶向治疗联合”时代即将来临。针对内分泌治疗耐药的药物研发集中在细胞周期蛋白依赖性激酶4/6抑制剂、组蛋白去乙酰化酶抑制剂以及磷脂酰肌醇3激酶-蛋白激酶B-雷帕霉素哺乳动物靶点(PI3K-AKT-mTOR)通路中的药物靶点抑制剂,为HR阳性MBC提供了新策略。探索生物标志物以指导靶向药物在MBC内分泌治疗中的更精准应用是当前及未来研究的重点。