Competitive evolution of NSCLC tumor clones and the drug resistance mechanism of first-generation EGFR-TKIs in Chinese NSCLC patients

作者：Qinfang Deng, Boxiong Xie, Leilei Wu, Xianxiu Ji, Chao Li, Feng Li, Qiyu Fang, Yuchen Bao, Jialu Li, Shengnan Jin, Chunming Ding, Yixue Li, Songwen Zhou · 发表于：Heliyon · 年份：2018 · DOI：10.1016/j.heliyon.2018.e01031 · 被引用次数：41 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Genomics and Diagnostics、RNA modifications and cancer

Purpose Although many studies have reported on the resistance mechanism of first-generation EGFR TKIs (1 st EGFR TKIs) treatment, large-scale dynamic ctDNA mutation analysis based on liquid biopsy for non-small cell lung cancer (NSCLC) in the Chinese population is rare. Using in-depth integration and analysis of ctDNA genomic mutation data and clinical data at multiple time points during the treatment of 53 NSCLC patients, we described the resistance mechanisms of 1 st EGFR TKIs treatment more comprehensively and dynamically. The resulting profile of the polyclonal competitive evolution of the tumor provides some new insights into the precise treatment of NSCLC. Experimental design A prospective study was conducted in patients with advanced NSCLC with acquired resistance to erlotinib, gefitinib or icotinib. By liquid biopsy, we detected mutations in 124 tumor-associated genes in the context of drug resistance. These 124 genes covered all tumor therapeutic targets and related biological pathways. During the entire course of treatment, the interval between two liquid biopsies was two months. Results Unlike the common mutations tested in tissue samples, our data showed a higher coverage of tumor heterogeneity (32.65%), more complex patterns of resistance and some new resistance mutation sites, such as EGFR p.V769M and KRAS p.A11V. The major resistance-associated mutations detected were still EGFR p.T790M (45.28%), other point mutations in EGFR (33.9%), and KRAS and NRAS mutation...