Mechanisms of Innate and Acquired Resistance to Anti-EGFR Therapy: A Review of Current Knowledge with a Focus on Rechallenge Therapies

被引：95

作者：

Parseghian, Christine M. ^{[1
]}

Napolitano, Stefania ^{[1
]}

Loree, Jonathan M. ^{[2
]}

Kopetz, Scott ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Div Canc Med, Houston, TX 77030 USA

[2] BC Canc, Vancouver, BC, Canada

来源：

CLINICAL CANCER RESEARCH | 2019年 / 25卷 / 23期

关键词：

METASTATIC COLORECTAL-CANCER; K-RAS MUTATIONS; FOLFIRI PLUS CETUXIMAB; CIRCULATING TUMOR DNA; PHASE-II TRIAL; TARGETED THERAPY; 1ST-LINE TREATMENT; MOLECULAR LANDSCAPE; GENOMIC LANDSCAPE; CLONAL SELECTION;

D O I：

10.1158/1078-0432.CCR-19-0823

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Innate and acquired resistance to anti-EGFR therapy (EGFRi) is a major limitation in the treatment of metastatic colorectal cancer (mCRC). Although RAS genes are the most commonly mutated innate and acquired oncogenes in cancer, there are a number of other mechanisms that limit the effectiveness of EGFRi. Patients with innate resistance have been found to contain BRAFV600E mutations, and possibly MET, MEK, PIK3CA, PTEN, and HER2 alterations. Meanwhile, BRAFV600E mutations may also be involved in acquired resistance to EGFRi, in addition to EGFR ectodomain mutations, MET alterations, and possibly HER2 amplification. In addition, paracrine effects and cell-fate mechanisms of resistance are being increasingly described as contributing to acquired resistance. Utilization of circulating tumor DNA has been paramount in monitoring the dynamic nature of acquired resistance and has helped to guide treatment decisions, particularly in the EGFRi rechallenge setting. Herein, we provide an in-depth review of EGFRi-resistance mechanisms and describe the current therapeutic landscape in the hopes of identifying effective rechallenge strategies.

引用

页码：6899 / 6908

页数：10

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