Emerging Molecular Dependencies of Mutant EGFR-Driven Non-Small Cell Lung Cancer

被引：12

作者：

Farnsworth, Dylan A. ^{[1
]}

Chen, Yankuan T. ^{[1
]}

de Rappard Yuswack, Georgia ^{[1
]}

Lockwood, William W. ^{[1
,2
]}

机构：

[1] BC Canc Res Inst, Dept Integrat Oncol, Vancouver, BC V5Z 1L3, Canada

[2] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 1Z7, Canada

来源：

CELLS | 2021年 / 10卷 / 12期

基金：

加拿大健康研究院;

关键词：

EGFR; TKI; lung cancer; functional genomics; CRISPR screens; EPIDERMAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITORS; NF-KAPPA-B; FACTOR RECEPTOR; ACQUIRED-RESISTANCE; BETA-CATENIN; SIGNALING PATHWAYS; GENETIC MODIFIERS; TUMOR-CELLS; OPEN-LABEL;

D O I：

10.3390/cells10123553

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Epidermal growth factor receptor (EGFR) mutations are the molecular driver of a subset of non-small cell lung cancers (NSCLC); tumors that harbor these mutations are often dependent on sustained oncogene signaling for survival, a concept known as "oncogene addiction". Inhibiting EGFR with tyrosine kinase inhibitors has improved clinical outcomes for patients; however, successive generations of inhibitors have failed to prevent the eventual emergence of resistance to targeted agents. Although these tumors have a well-established dependency on EGFR signaling, there remain questions about the underlying genetic mechanisms necessary for EGFR-driven oncogenesis and the factors that allow tumor cells to escape EGFR dependence. In this review, we highlight the latest findings on mutant EGFR dependencies, co-operative drivers, and molecular mechanisms that underlie sensitivity to EGFR inhibitors. Additionally, we offer perspective on how these discoveries may inform novel combination therapies tailored to EGFR mutant NSCLC.

引用

页数：25

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