Tumor Microenvironment Induced Egfr-Tki Resistance

Lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation could be treated by EGFR-tyrosine kinase inhibitor (EGFR-TKI), and the treatment is very effective in most patients. However, some patient with EGFR mutation, but the EGFR-TKI treatment is less effective, and cause clinical treatment failure. Tumor microenvironment play an important role to interact with cancer cells, and result in tumor progression, invasion and metastasis. Our previous study showed tumor-associated macrophages (TAMs) is an independent risk factor to poor treatment response and prognosis. However, the mechanisms are still unknown. In this 2-year study, we will use co-culture system with MDM-TAMs and cancer cells to identify the pathway inducing EGFR-TKI resistance through microarray and proteomic studies. We will focus on candidate pathways and underlying mechanisms. Primary alveolar macrophages from lung cancer patient will be collected for evaluation of primary TAMs function and phenotype, as well as the function to attenuate EGFR-TKI. The results of this study could provide our future direction for better and more effective pathway for lung adenocarcinoma patients.