《生命科学》 2022, 34(12): 1559-1568

雌激素受体阳性乳腺癌内分泌治疗耐药机制及靶向治疗策略

牟　园^1,2 , 熊　昱² , 秦　烨^1,2,*

¹肿瘤微环境与免疫治疗湖北省重点实验室(三峡大学)，宜昌 443000 ²三峡大学医学院，宜昌 443000

摘　要：

乳腺癌是中国女性最常见的恶性肿瘤之一。内分泌治疗是雌激素受体(estrogen receptor, ER) 阳性乳腺癌有效的治疗手段之一，也是最常用的方法，主要包括选择性雌激素受体调节剂(selective estrogen receptor modulators, SERMs)、芳香化酶抑制剂(aromatase inhibitors, AIs)、选择性雌激素受体下调剂(selective estrogen receptor down regulators, SERDs)。尽管内分泌治疗增加了患者生存率，但耐药问题也极大地影响了 乳腺癌患者的预后。越来越多的耐药机制被报道，如ESR1 突变、受体酪氨酸激酶改变、细胞信号通路、表观遗传调控、代谢重编程、肿瘤干细胞、肿瘤微环境改变等。该文对近几年报道的乳腺癌内分泌治疗耐药机制及靶向治疗策略进行详细的综述。

通讯作者：秦　烨 , Email:ycqinye@163.com

Endocrine therapy resistance mechanism and targeted therapy strategy for estrogen receptor-positive breast cancer

MOU Yuan^1,2 , XIONG Yu² , QIN Ye^1,2,*

¹Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang 443000, China ²Medical College, China Three Gorges University, Yichang 443000, China

Abstract:

Breast cancer is one of the most common malignant tumors in Chinese women. Endocrine therapy is one of the effective treatments for estrogen receptor positive (ER) breast cancer, and it is also the most commonly used method, mainly including selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and selective estrogen receptor down regulators (SERDs). Although endocrine therapy increases patient survival, the problem of drug resistance greatly affects the prognosis of breast cancer patients. More and more mechanisms of drug resistance are being reported, such as ESR1 mutations, altered receptor tyrosine kinases, cellular signaling pathways, epigenetic regulation, metabolic reprogramming, tumor stem cells and altered tumor microenvironment. This paper provides a detailed review of the mechanisms of endocrine therapy resistance and targeted treatment strategies for breast cancer in recent years.

Communication Author：QIN Ye , Email:ycqinye@163.com