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Cotargeting EGFR and autophagy signaling: A novel therapeutic strategy for non‑small‑cell lung cancer (Review)

Cotargeting EGFR and autophagy signaling: A novel therapeutic strategy for non‑small‑cell lung... epidermal growth factor receptor (EGFR) somatic mutations are found in the majority of non‑small‑cell lung cancers (NSCLCs) and patients with NSCLC who harbor EGFR mutations have been shown to exhibit increased sensitivity to the small‑molecule EGFR‑tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. However, the majority of tumors develop acquired resistance to EGFR‑TKIs after a median of 10‑16 months, which limits the clinical efficacy of these drugs. Autophagy, an important homeostatic cellular recycling mechanism, has emerged as a potential target for the acquired resistance phenotype. Recently, several studies demonstrated that autophagy may be induced in a dose‑dependent manner by treatment of multiple cancer cell lines with EGFR‑TKIs in vitro. Furthermore, it was recently reported that autophagy, as a cytoprotective response, may be activated by EGFR‑TKIs in lung cancer cells and that the inhibition of autophagy enhanced the cytotoxic effect of EGFR‑TKIs. In this review, we aimed to focus on the association between resistance to EGFR‑TKIs and autophagy, and assess whether autophagy inhibition represents a promising approach to improve the efficacy of EGFR‑TKIs in the treatment of NSCLC patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Clinical Oncology Spandidos Publications

Cotargeting EGFR and autophagy signaling: A novel therapeutic strategy for non‑small‑cell lung cancer (Review)

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Publisher
Spandidos Publications
Copyright
Copyright © Spandidos Publications
ISSN
2049-9450
eISSN
2049-9469
DOI
10.3892/mco.2013.187
Publisher site
See Article on Publisher Site

Abstract

epidermal growth factor receptor (EGFR) somatic mutations are found in the majority of non‑small‑cell lung cancers (NSCLCs) and patients with NSCLC who harbor EGFR mutations have been shown to exhibit increased sensitivity to the small‑molecule EGFR‑tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. However, the majority of tumors develop acquired resistance to EGFR‑TKIs after a median of 10‑16 months, which limits the clinical efficacy of these drugs. Autophagy, an important homeostatic cellular recycling mechanism, has emerged as a potential target for the acquired resistance phenotype. Recently, several studies demonstrated that autophagy may be induced in a dose‑dependent manner by treatment of multiple cancer cell lines with EGFR‑TKIs in vitro. Furthermore, it was recently reported that autophagy, as a cytoprotective response, may be activated by EGFR‑TKIs in lung cancer cells and that the inhibition of autophagy enhanced the cytotoxic effect of EGFR‑TKIs. In this review, we aimed to focus on the association between resistance to EGFR‑TKIs and autophagy, and assess whether autophagy inhibition represents a promising approach to improve the efficacy of EGFR‑TKIs in the treatment of NSCLC patients.

Journal

Molecular and Clinical Oncology – Spandidos Publications

Published: Jan 1, 2014

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