Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, PR China.
Department of Oncology, Mayo Clinic, Rochester, MN, United States.
Biochim Biophys Acta Rev Cancer. 2017 Aug;1868(1):148-156. doi: 10.1016/j.bbcan.2017.03.008. Epub 2017 Mar 23.
Based on the prominent role estrogen receptor (ER) plays in breast cancer, endocrine therapy has been developed to block the ER pathway and has shown great effectiveness. Fulvestrant, the first selective ER down-regulator (SERD), was demonstrated to completely suppress ERα and notably efficient. However, resistance to fulvestrant occurs, either intrinsic or acquired during the treatment. Several potential mechanisms inducing fulvestrant resistance have been proposed, composed of activated ERα-independent compensatory growth factor signaling, stimulated downstream kinases, altered cell cycle mediators, etcetera. Experimentally, combinations of fulvestrant with targeted treatments were reported to eliminate the resistance and improve the effect of fulvestrant. Meanwhile, some clinical trials associated with the targeted combination therapies are in progress. This review focuses on the underlying mechanisms that contribute to fulvestrant resistance in ER-positive breast cancer and provides an overview of combined fulvestrant with targeted agents to shed light on optimal therapies for patients with ER-positive breast cancer.
基于雌激素受体 (ER) 在乳腺癌中发挥的重要作用，已经开发出内分泌疗法来阻断 ER 通路，并且已经显示出了极大的效果。氟维司群是第一个选择性 ER 下调剂 (SERD)，它被证明能够完全抑制 ERα，并且效果显著。然而，在治疗过程中，无论是内在的还是获得性的，都会对氟维司群产生耐药性。已经提出了几种潜在的诱导氟维司群耐药的机制，包括激活 ERα 非依赖性补偿性生长因子信号、刺激下游激酶、改变细胞周期调节剂等。实验上，已经报道了氟维司群与靶向治疗的联合使用可以消除耐药性并提高氟维司群的效果。同时，一些与靶向联合治疗相关的临床试验正在进行中。这篇综述重点关注了导致 ER 阳性乳腺癌中氟维司群耐药的潜在机制，并概述了氟维司群与靶向药物的联合使用，为 ER 阳性乳腺癌患者的最佳治疗提供了思路。
