Therapeutic resistance in cancer: microRNA regulation of EGFR signaling networks

作     者：German G.Gomez Jill Wykosky Ciro Zanca Frank B.Furnari Webster K.Cavenee 

作者机构：Ludwig Institute for Cancer Research University of California San Diego 

出 版 物：《Cancer Biology & Medicine》 (癌症生物学与医学（英文版）)

年 卷 期：2013年第10卷第4期

页      面：192-205页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by An American Brain Tumor Association Basic Research grant to G.G.G. in memory of Keith Powers, P01-CA95616, R01-NS080939 James S. McDonnell Foundation 

主　　题：表皮生长因子受体 microRNA 治疗药物 癌症患者 信号网络 抗药性 受体抑制剂 受体酪氨酸激酶 

摘      要：Receptor tyrosine kinases(RTKs)such as the epidermal growth factor receptor(EGFR)regulate cellular homeostatic *** activates downstream signaling cascades that promote tumor cell survival,proliferation and *** of EGFR signaling as a consequence of overexpression,amplification and mutation of the EGFR gene occurs frequently in several types of cancers and many become dependent on EGFR signaling to maintain their malignant ***,concerted efforts have been mounted to develop therapeutic agents and strategies to effectively inhibit ***,limited therapeutic benefits to cancer patients have been derived from EGFR-targeted therapies.A well-documented obstacle to improved patient survival is the presence of EGFR-inhibitor resistant tumor cell variants within heterogeneous tumor cell ***,we summarize the mechanisms by which tumors resist EGFR-targeted therapies and highlight the emerging role of microRNAs(miRs)as downstream effector molecules utilized by EGFR to promote tumor initiation,progression and that play a role in resistance to EGFR *** also examine evidence supporting the utility of miRs as predictors of response to targeted therapies and novel therapeutic agents to circumvent EGFR-inhibitor resistance mechanisms.