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: Yuan-Yuan Li, Sze-Kwan Lam, Chun-Yan Zheng, James Chung-Man Ho
• Journal: Journal of Cancer (J Cancer) Vol. 6 Issue 4 Pg. 382-6 ( 2015) ISSN: 1837-9664 [Print] Australia
• PMID: 25767609 (Publication Type: Journal Article)