Farnesyltransferase inhibition overcomes the adaptive resistance to targeted therapies in oncogene-addicted non-small cell lung cancer II

Drug-tolerance has emerged as one of the major non-genetic adaptive processes driving resistance to targeted therapy (TT) in non-small cell lung cancer (NSCLC). However, the kinetics and sequence of molecular events governing this adaptive response remain poorly understood. Here, we performed transcriptomic profiling by RNAseq in a panel of EGFR-mutant NSCLC cell lines (PC9, HCC4006, H3255 and HCC827) that were previously subcloned to minimize the presence of potential pre-existing resistant cells. Cells were treated by either erlotinib (1 µM) or osimertinib (1 µM) for a short period (24h), until drug-tolerance (between 7 and 21 days), and until development of fully resistant proliferative cells (RPC).