title: Cotargeting EGFR and autophagy signaling: A novel therapeutic strategy for non-small-cell lung cancer.
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-TKIsin 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.
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangshou, Zhejiang;
authors.forename: Xinbing
authors.initials: X
authors.lastname: Sui
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangshou, Zhejiang;
authors.forename: Na
authors.initials: N
authors.lastname: Kong
authors.affiliation: Department of Nephrology, Hebei Medical University Affiliated North China Petroleum Bureau General Hospital, Renqiu, Hebei;
authors.forename: Minghua
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangshou, Zhejiang;
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangshou, Zhejiang;
authors.forename: Fang
authors.initials: F
authors.lastname: Lou
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangshou, Zhejiang; ; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangshou, Zhejiang; ; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, P.R. China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Pan
keywords: autophagy; epidermal growth factor receptor; non-small-cell lung cancer; resistance