ATR and cancer: ATM and ATR have been reported to share a synthetic lethal relationship in some cancer types.17–19,37,38 However, it has become increasingly clear that most synthetic lethal interactions depend highly on the genetic background in which they are studied.39 By targeting ATM through multiple methods, our data indicate that complete loss of ATM function is necessary to sensitise PDAC cells to AZD6738 or the AZD6738 and gemcitabine combination.