Because PARPi are approved for the treatment of cancers that have homologous-recombination defects and trapped PARP1 is the key cytotoxic event in homologous recombination-defective cells, we assessed the effect of combined exposure to CB-5083 + talazoparib in DLD1 cells with/without genetic ablation of BRCA2. When used alone, CB-5083 had a modest BRCA2 synthetic lethal effect (Extended Data Fig. 9e), but it had a far greater effect on BRCA2–/– DLD1 cells than isogenic wild-type BRCA2 (BRCA2WT) cells when used in combination with talazoparib (Fig. 6f and Extended Data Fig. 9f,g). The gene discussed is PARP1; the disease is cancer.