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Mechanisms of resistance to EGFR tyrosine kinase inhibitors: implications for patient selection and drug combination strategies

Mechanisms of resistance to EGFR tyrosine kinase inhibitors: implications for patient selection... The receptor for epidermal growth factor (EGFR, ErbB1, HER1) supports the growth and maintenance of a broad range of human tumor types, and EGFR-targeting drugs are approved for the treatment of several advanced stage cancers, including non-small cell lung cancer (NSCLC), pancreatic cancer, squamous cell cancer of the head and neck (SCCHN), and colorectal cancer. Recent years have witnessed significant advances in our understanding of dysregulated signal transduction in cancer cells resulting from changes in the expression and/or mutational status of key signaling molecules that modulate sensitivity to drugs targeting EGFR. Based on this knowledge, we have an exciting opportunity to maximize the benefit provided to cancer patients by EGFR inhibitors. In this review article, we describe molecular determinants of sensitivity or resistance to EGFR-targeted agents, with specific emphasis on EGFR tyrosine kinase inhibitors (TKIs). The impact of these findings on our ability to evaluate candidate predictive biomarkers and to design robust mechanism-based combination strategies is also discussed. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Targeted Oncology Springer Journals

Mechanisms of resistance to EGFR tyrosine kinase inhibitors: implications for patient selection and drug combination strategies

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References (79)

Publisher
Springer Journals
Copyright
Copyright © 2008 by The Author(s)
Subject
Medicine & Public Health; Biomedicine general; Oncology
ISSN
1776-2596
eISSN
1776-260X
DOI
10.1007/s11523-008-0093-6
Publisher site
See Article on Publisher Site

Abstract

The receptor for epidermal growth factor (EGFR, ErbB1, HER1) supports the growth and maintenance of a broad range of human tumor types, and EGFR-targeting drugs are approved for the treatment of several advanced stage cancers, including non-small cell lung cancer (NSCLC), pancreatic cancer, squamous cell cancer of the head and neck (SCCHN), and colorectal cancer. Recent years have witnessed significant advances in our understanding of dysregulated signal transduction in cancer cells resulting from changes in the expression and/or mutational status of key signaling molecules that modulate sensitivity to drugs targeting EGFR. Based on this knowledge, we have an exciting opportunity to maximize the benefit provided to cancer patients by EGFR inhibitors. In this review article, we describe molecular determinants of sensitivity or resistance to EGFR-targeted agents, with specific emphasis on EGFR tyrosine kinase inhibitors (TKIs). The impact of these findings on our ability to evaluate candidate predictive biomarkers and to design robust mechanism-based combination strategies is also discussed.

Journal

Targeted OncologySpringer Journals

Published: Oct 24, 2008

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