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

Sui,Xinbing; Kong,Na; Zhu,Minghua; Wang,Xian; Lou,Fang; Han,Weidong; Pan,Hongming

doi:10.3892/mco.2013.187

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

Authors:
- Xinbing Sui
- Na Kong
- Minghua Zhu
- Xian Wang
- Fang Lou
- Weidong Han
- Hongming Pan
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Affiliations: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangshou, Zhejiang, P.R. China, Department of Nephrology, Hebei Medical University Affiliated North China Petroleum Bureau General Hospital, Renqiu, Hebei, P.R. China
Published online on: September 18, 2013 https://doi.org/10.3892/mco.2013.187
Pages: 8-12

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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.

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