MOLT-4 radiosensitization by VE-821

DNA damage induction by either radio- or chemo-therapy has been the most widely used approach in cancer therapy, exploiting the genomic instability of cancer cells. A promising strategy takes advantage of tumour specific abnormalities in DNA damage response. Inhibition of the ATR/Chk1 pathway has been shown to be synthetically lethal in cells with high levels of oncogene-induced replication stress and in p53- or ATM- deficient cells. In the presented study, we aimed to elucidate molecular mechanisms underlying radiosensitization of MOLT-4 cells by VE-821, a higly potent and specific inhibitor of ATR. We combined multiple approaches: cell biology techniques to reveal the inhibitor-induced phenotypes, and quantitative proteomics, phosphoproteomics, and metabolomics to comprehensively describe drug-induced changes in irradiated cells.