MTE21.01 Next Generation Sequencing

Abstract

Non-small cell lung cancer (NSCLC) with sensitive epidermal growth factor receptor (EGFR) mutations invariably develop resistance to EGFR tyrosine kinase inhibitors (TKIs). 20%-30% of NSCLC patients harboring sensitive mutations have no good initial clinical response to EGFR-TKIs, which is defined as having intrinsic resistance to EGFR-TKIs; while the rest of patients with activating mutations who are initially responsive to EGFR-TKIs eventually develop acquired resistance after 10–12 months of consistent clinical benefit, followed by disease progression. The drug resistance is a really tough and urgent clinical problem. Part of resistant mechanisms have been reported, including BIM deletion polymorphism, combined with other bypass signal pathway activation, epithelial-mesenchymal transition (EMT) for primary resistance; T790M, cMET amplification, SCLC transformation for acquired resistance. However, partial resistant mechanisms still unknown. In contrast to acquired resistance to EGFR-TKIs, intrinsic resistance is more complicated. Next-generation sequencing (NGS) is a promising tool for analysis of tumor mutations. We aimed to investigate the intrinsic resistant mechanisms to EGFR-TKIs by NGS, further to optimize treatment strategies and improve clinical outcome in EGFR activating mutant patients having intrinsic resistance to EGFR-TKIs. At present, the study is underway, and the results will be presented at the 2016 WCLC. next-generation sequencing, NSCLC, EGFR-TKIs, drug resistance