Drug-tolerant persister cancer cells

Drug resistance continues to be a major bottleneck of curing patients with cancer.Two primary intracellular factors contribute to emergence of drug resistance in treatment-naïve cancer cells,which are a popu-lation of malignant cells not receiving any therapy before.One is that genetic mutations occur in key cancer-addicted genes,such as T790M in epidermal growth factor receptor(EGFR),are a critical mechanism underlying some therapeutic resistance,thus boosting the development and usage of targeted inhibitors to benefit patients with cancer.In addi-tion,non-genetic factors,including aberrant epigenetic/metabolic ma-chinery and/or reprogrammed transcription profile,probably play more important roles in drug resistance in cancer cells.1 Upon receiving treat-ment with osimertinib,a subset of EGFR-mutated lung cancer cells ac-quired resistance to osimertinib through mammalian SWI/SNF complex-mediated alterations in chromatin accessibility to sustain low cellular ROS level and hyperproliferation,but no new mutations occurred in EGFR.