New Strategies in Overcoming Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Lung Cancer

被引：304

作者：

Oxnard, Geoffrey R. ^{[3
,4
]}

Arcila, Maria E. ^{[2
]}

Chmielecki, Juliann ^{[2
]}

Ladanyi, Marc ^{[2
]}

Miller, Vincent A. ^{[1
,2
]}

Pao, William ^{[5
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, Dept Med, New York, NY 10021 USA

[2] Weill Cornell Med Coll, New York, NY USA

[3] Dana Farber Canc Inst, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Boston, MA USA

[5] Vanderbilt Ingram Canc Ctr, Nashville, TN USA

来源：

CLINICAL CANCER RESEARCH | 2011年 / 17卷 / 17期

关键词：

PHASE-II TRIAL; LEPTOMENINGEAL METASTASES; DRUG-RESISTANCE; T790M MUTATION; EGFR; CELL; GEFITINIB; ERLOTINIB; TUMORS; SENSITIVITY;

D O I：

10.1158/1078-0432.CCR-10-2571

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The management of non-small cell lung carcinoma (NSCLC) has been transformed by the observation that lung adenocarcinomas harboring mutations in epidermal growth factor receptor (EGFR) are uniquely sensitive to EGFR tyrosine kinase inhibitors (TKI). In these patients, acquired resistance to EGFR-TKI develops after a median of 10 to 14 months, at which time the current standard practice is to switch to conventional cytotoxic chemotherapy. Several possible mechanisms for acquired resistance have been identified, the most common being the development of an EGFR T790M gatekeeper mutation in more than 50% of cases. In this review, we discuss recent advances in the understanding of acquired TKI resistance in EGFR-mutant lung cancer and review therapeutic progress with second generation TKIs and combinations of targeted therapies. Clin Cancer Res; 17(17); 5530-7. (C) 2011 AACR.

引用

页码：5530 / 5537

页数：8

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