Therapeutic resistance in cancer: microRNA regulation of EGFR signaling networks

查看全文 作　　者：German [1]G.Gomez;Jill [1]Wykosky;Ciro [1]Zanca;Frank [1]B.Furnari;Webster [1]K.Cavenee

机构地区：[1]Ludwig Institute for Cancer Research, University of California San Diego

出　　处：《Cancer Biology & Medicine》索引2013年第10卷第4期,共14页

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 摘　　要：Receptor tyrosine kinases(RTKs)such as the epidermal growth factor receptor(EGFR)regulate cellular homeostatic processes.EGFR activates downstream signaling cascades that promote tumor cell survival,proliferation and migration.Dysregulation 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 phenotypes.Consequently,concerted efforts have been mounted to develop therapeutic agents and strategies to effectively inhibit EGFR.However,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 masses.Here,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 inhibitors.We 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. 关键词：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

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Therapeutic resistance in cancer: microRNA regulation of EGFR signaling networks

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