PBRM1 and cancer: Thus, the loss of SMARCA4 could impair DNA repair and enhance intrinsic replication stress through multiple mechanisms, possibly explaining the specific association between SMARCA4 deficiency and ATR inhibitor efficacy in LUAD cells, although we do not exclude possibilities that loss of ARID1A or PBRM1 could also serve as biomarkers for ATRi-based therapy in other cancer types.