The scientific rationale for this combination lies in the complementary mechanisms of action between the two agents: trastuzumab deruxtecan selectively delivers a cytotoxic topoisomerase I inhibitor to HER2-expressing tumor cells, leading to DSBs, while AZD6738 inhibits the ATR-mediated DDR, thereby impairing the tumor’s ability to repair RS and DNA lesions. This evidence concerns the gene ATR and neoplasm.