激素受体阳性乳腺癌靶向治疗进展

Advances of target therapy in hormone-receptor-positive breast cancer

内分泌治疗是激素受体阳性乳腺癌的主要治疗手段。内分泌耐药是这部分患者肿瘤复发或进展的主要原因。近期研究发现一系列导致激素受体阳性乳腺癌不依赖雌激素的抵抗机制,开发出相应的靶向治疗药物,其中包括细胞周期蛋白依赖性激酶4/6抑制剂、mTOR抑制剂、表皮生长因子受体抑制剂、抗血管生成药物、组蛋白去乙酰化酶抑制剂、成纤维细胞生长因子受体抑制剂、胰岛素样生长因子受体抑制剂,以及免疫检查点抑制剂等。这些药物被用于阻断耐药通路并提高内分泌治疗疗效,其中已经被批准上市的靶向药物有依维莫司和palbociclib。本文将对内分泌联合靶向治疗的药物研究进展进行综述。

Hormone therapy is a major treatment option for hormone-receptor-positive （HR＋） breast cancer. Resistance to hormone therapy is the major reason for disease recurrence and progression. Recent studies have identified several resistance mechanisms that lead to the estrogen-independent growth of HR＋breast cancer and were exploited to develop novel target drugs, including cyclin-de-pendent kinases 4 and 6 （CDK4/6） inhibitor, mammalian target of rapamycin （mTOR） inhibitor, epidermal growth factor receptor family inhibitor, vascular endothelial growth factor inhibitor, histone deacetylase inhibitor, fibroblast growth factor receptor inhibitor, insulin-like growth factor receptor inhibitor, and checkpoint inhibitor. These inhibitors are being developed to block resistance pathways and improve the efficacy of hormonal therapy. Among these drugs, the mTOR inhibitor everolimus and the CDK4/6 inhibitor palbociclib are currently approved in the United States to treat metastatic HR＋breast cancer. In this study, we summarize the frontier advances in the combination of hormone and target therapies.