Overcoming resistance to tyrosine kinase inhibitors: Lessons learned from cancer cells treated with EGFR antagonists

Brent N. Rexer; Jeffrey A. Engelman; Carlos L. Arteaga

doi:10.4161/cc.8.1.7324

Overcoming resistance to tyrosine kinase inhibitors: Lessons learned from cancer cells treated with EGFR antagonists

Brent N. Rexer, Jeffrey A. Engelman, Carlos L. Arteaga

Research output: Contribution to journal › Review article › peer-review

67 Scopus citations

Abstract

Tyrosine kinase inhibitors (TKIs) are effective anti-cancer therapies but resistance to these agents eventually develops. Several models of resistance to TKIs have been studied including resistance to EGFR inhibitors. Recent studies in EGFR-dependent A431 cells found upregulation of the IGF1R pathway as a mechanism to overcome blockade of EGFR. This was associated with amplification of IGF1R signaling and recovery of downstream PI3K-AKT activation. This work adds to a growing body of cell lines in culture that have provided insights into mechanisms of resistance that can be interrogated in primary tumors in patients. In this review, these model systems and their applicability to human cancers, as well as strategies to identify and overcome resistance to TKIs, are discussed.

Original language	English (US)
Pages (from-to)	18-22
Number of pages	5
Journal	Cell Cycle
Volume	8
Issue number	1
DOIs	https://doi.org/10.4161/cc.8.1.7324
State	Published - Jan 1 2009

Keywords

Breast cancer
EGFR
HER2
PI3K
TKI resistance
Tyrosine kinase inhibitors

ASJC Scopus subject areas

Molecular Biology
Developmental Biology
Cell Biology

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title = "Overcoming resistance to tyrosine kinase inhibitors: Lessons learned from cancer cells treated with EGFR antagonists",

abstract = "Tyrosine kinase inhibitors (TKIs) are effective anti-cancer therapies but resistance to these agents eventually develops. Several models of resistance to TKIs have been studied including resistance to EGFR inhibitors. Recent studies in EGFR-dependent A431 cells found upregulation of the IGF1R pathway as a mechanism to overcome blockade of EGFR. This was associated with amplification of IGF1R signaling and recovery of downstream PI3K-AKT activation. This work adds to a growing body of cell lines in culture that have provided insights into mechanisms of resistance that can be interrogated in primary tumors in patients. In this review, these model systems and their applicability to human cancers, as well as strategies to identify and overcome resistance to TKIs, are discussed.",

keywords = "Breast cancer, EGFR, HER2, PI3K, TKI resistance, Tyrosine kinase inhibitors",

author = "Rexer, {Brent N.} and Engelman, {Jeffrey A.} and Arteaga, {Carlos L.}",

note = "Funding Information: Supported in part by NCI R01 CA62212 (C.L.A.), R01 CA80195 (C.L.A.), ACS Clinical Research Professorship Grant CRP-07-234 (C.L.A.), a grant from the Entertainment Industry Foundation (C.L.A.), NCI T32 CA119910 (B.N.R.), Breast Cancer Specialized Program of Research Excellence (SPORE) P50 CA98131, Vanderbilt-Ingram Comprehensive Cancer Center Support Grant P30 CA68485, NIH K08 grant CA120060-01 (J.A.E.), an American Association for Cancer Research Grant (J.A.E.), the DF/HCC Lung Cancer Specialized Program SPORE grant P50 CA090578 (J.A.E.), and the DF/HCC Gastrointestinal Cancer SPORE grant P50 CA127003 (J.A.E).",

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doi = "10.4161/cc.8.1.7324",

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AU - Arteaga, Carlos L.

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PY - 2009/1/1

Y1 - 2009/1/1

N2 - Tyrosine kinase inhibitors (TKIs) are effective anti-cancer therapies but resistance to these agents eventually develops. Several models of resistance to TKIs have been studied including resistance to EGFR inhibitors. Recent studies in EGFR-dependent A431 cells found upregulation of the IGF1R pathway as a mechanism to overcome blockade of EGFR. This was associated with amplification of IGF1R signaling and recovery of downstream PI3K-AKT activation. This work adds to a growing body of cell lines in culture that have provided insights into mechanisms of resistance that can be interrogated in primary tumors in patients. In this review, these model systems and their applicability to human cancers, as well as strategies to identify and overcome resistance to TKIs, are discussed.

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Overcoming resistance to tyrosine kinase inhibitors: Lessons learned from cancer cells treated with EGFR antagonists

Abstract

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