曲妥珠单抗耐药后HER-2阳性转移性乳腺癌靶向治疗策略

Targeted therapeutic strategies of HER-2 positive metastatic breast cancer after trastuzumab resistance

人表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)是一种跨膜酪氨酸激酶受体,可以激活下游一系列信号通路,导致肿瘤细胞增殖和存活。HER-2阳性乳腺癌是乳腺癌的特殊类型,恶性程度高,预后差。抗HER-2单克隆抗体曲妥珠单抗能够改善该类乳腺癌治疗效果,但最终仍难逃耐药的结局。近年来,针对曲妥珠单抗耐药机制的研究、新型靶向药物的研发以及治疗策略的探索,在克服曲妥珠单抗耐药性方面取得了重大进展,本文将对其耐药后治疗策略及临床试验数据进行综述。

Human epidermal growth factor receptor 2(HER-2)is a transmembrane tyrosine kinase receptor which can activate the downstream signaling pathways,leading to proliferation and survival of cancer cells.HER-2 positive breast cancer is a special subtype of breast cancer with high malignancy and poor prognosis.Trastuzumab,an anti-HER-2 monoclonal antibody,is able to improve the treatment efficacy of this kind of cancer,but could not escape the ending of resistance ultimately.In recent years,researches on mechanism of trastuzumab resistance,development of novel targeted drugs and exploration of the treatment strategies have made significant progress in overcoming the resistance of trastuzumab.This article is going to introduce strategies of targeted therapy and also the data of clinical trials focusing on the treatment against trastuzumab resistance.