Olaparib-resistant gastric cancer cells show the compensatory alterations in DNA-damage response pathways, and exhibit cross-resistance to cisplatin; however, these cells are highly sensitive to subsequent treatment with irinotecan through tyrosyl-DNA phosphodiesterase 1 (TDP1) downregulation with increased topoisomerase 1 (TOP1) activity. Here, TOP1 is linked to gastric cancer.