埃罗替尼
癌症研究
肺癌
体内
癌症
酪氨酸激酶
医学
敏化
顺铂
表皮生长因子受体
药理学
激酶
酪氨酸激酶抑制剂
野生型
化学
肿瘤科
生物
突变体
免疫学
内科学
化疗
受体
生物化学
生物技术
基因
作者
Judith Raimbourg,Marie‐Pierre Joalland,Mathilde Cabart,Ludmilla de Plater,Fanny Bouquet,Ariel Savina,Didier Decaudin,Jaafar Bennouna,François M. Vallette,Lisenn Lalier
出处
期刊:Molecular Cancer Therapeutics
[American Association for Cancer Research]
日期:2017-05-19
卷期号:16 (8): 1634-1644
被引量:19
标识
DOI:10.1158/1535-7163.mct-17-0075
摘要
Abstract The benefit of EGFR–TKI in non–small cell lung cancer has been demonstrated in mutant EGFR tumors as first-line treatment but the benefit in wild-type EGFR tumors is marginal as well as restricted to maintenance therapy in pretreated patients. This work aimed at questioning the effects of cisplatin initial treatment on the EGFR pathway in non–small cell lung cancer and the functional consequences in vitro and in in vivo animal models of patient-derived xenografts (PDX). We establish here that cisplatin pretreatment specifically sensitizes wild-type EGFR-expressing cells to erlotinib, contrary to what happens in mutant EGFR cells and with a blocking EGFR antibody, both in vitro and in vivo. The sensitization entails the activation of the kinase Src upstream of EGFR, thereafter transactivating EGFR through a ligand-independent activation. We propose a combination of markers that enable to discriminate between the tumors sensitized to erlotinib or not in PDX models, which should be worth testing in patients. These markers might be useful for the selection of patients who would benefit from erlotinib as a maintenance therapy. Mol Cancer Ther; 16(8); 1634–44. ©2017 AACR.
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