title: The Effect of Tumor Microenvironment on Autophagy and Sensitivity to Targeted Therapy in EGFR-Mutated Lung Adenocarcinoma.
abstract: Lung cancer is the top cancer killer worldwide. Tyrosine kinase inhibitors (TKIs), for example erlotinib, are commonly used to target epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (ADC). Autophagy is a cellular response to stress, serving as a protective mechanism during anticancer therapy. The tumor microenvironment (TME) is composed of non-tumor cells that include fibroblasts. Our study aimed to investigate the effect of TME on autophagy and TKI sensitivity. Following cell sorting after direct co-culturing, autophagy and cytokine production were observed in both HCC827 and MRC-5 cells. The synergistic combination of erlotinib and chloroquine (autophagy inhibitor) was observed under TME. Tumor growth was significantly suppressed with combined erlotinib/chloroquine compared with erlotinib in HCC827 xenografts.
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR.
authors.forename: Sze-Kwan
authors.initials: SK
authors.lastname: Lam
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Zheng
authors.affiliation: Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR.
authors.forename: James Chung-Man
authors.initials: JC
authors.lastname: Ho
keywords: Tumor microenvironment; autophagy; non-small cell lung carcinoma; tyrosine kinase inhibitors