scRNA-seq data of Parental PC9, DTPs and DTEPs treated with/without NEO2734

Cancer cell can adapt through both genetic and non-genetic mechanisms to acquire drug resistance. Emerging evidence indicates the existence of drug tolerant persisters (DTPs) which survive targeted- or chemo- therapies through elusive non-mutational and reversible mechanisms. DTPs can resume proliferation and drug sensitivity after drug withdraw. They eventually acquire different genetic and non-genetic mechanism under continuous treatment to promote cancer regrowth. Better understanding their specific features could help to identify novel vulnerabilities of DTPs. In this study, compound screen and genetic screen were performed on drug tolerant persisters derived from PC9 cells treated with high dosage of EGFR inhibitor. Based on our screen results, we identified that Bet inhibition served as a promising approach to eradicate DTPs while have minor effect on parental cancer cells. scRNA seq were further performed to investigate the mechanism insights.