Drug tolerant persisters in erlotinib treated EGFR-mutated lung adenocarcinoma arise from pre-existing tumor cells and survive in an adapted stromal microenvironment. Drug tolerant persisters in erlotinib treated EGFR-mutated lung adenocarcinoma arise from pre-existing tumor cells and survive in an adapted stromal microenvironment

Targeted therapies require life-long treatment, as drug discontinuation invariably leads to tumor recurrence. Recurrence is thought to mainly be driven by minor subpopulations of drug tolerant persister (DTP) cells that survive the cytotoxic drug effect. In lung cancer, DTP studies have mainly been conducted using tumor cell line models. We conducted an in vivo DTP study using a lung adenocarcinoma (LUAD) patient-derived xenograft (PDX) tumor driven by an epidermal growth factor receptor (EGFR) mutation. Daily treatment of tumor-bearing mice for 5-6 weeks markedly shrunk the tumors and generated DTPs, which were analyzed by bulk population transcriptome. Overall design: Microarray transcriptome profiling was performed on 4 baseline (BL) and 4 DTP tumors; total RNAs from xenografts were amplified by DASL kit and hybridized to Illumina HT12v4 chip