ATR and non-small cell lung carcinoma: Highly expressed EMT-TFs such as ZEB1 and TWIST1 can directly bind to the intron region and promoter of BIM, in mesenchymal NSCLC cancer cells and repress its transcription.248,252 In addition, EMT-TFs can also activate the ATR serine/threonine kinase (ATR)- checkpoint kinase 1 (CHK1)-AuroraB signaling cascade, and Aurora B can phosphorylate and degrade BIM.253 In the absence of BIM, TKIs cannot induce apoptosis despite the effective inhibition of oncogenic pathways.