Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

被引：40

作者：

Alexander, Peter B. ^{[1
]}

Wang, Xiao-Fan ^{[1
]}

机构：

[1] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA

来源：

FRONTIERS OF MEDICINE | 2015年 / 9卷 / 02期

基金：

美国国家卫生研究院;

关键词：

targeted therapy; drug resistance; receptor tyrosine kinases; cancer; LUNG-CANCER; MET AMPLIFICATION; DRUG-RESISTANCE; ACQUIRED-RESISTANCE; TARGETED THERAPIES; EGFR T790M; GEFITINIB; GROWTH; REQUIREMENTS; MUTATIONS;

D O I：

10.1007/s11684-015-0396-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.

引用

页码：134 / 138

页数：5

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