/Cells displayed a spectrum of sensitivity to VE-821, PF-477736 and MK-1775 cytotoxicity. LC50 values varied 3.5-fold with VE-821 (0.6 to 2.1 μM), 5-fold with PF-477736 (22.4 to 125.5 nM) and 5-fold with MK-1775 (121.4 to 454.5 nM) (Fig. 2 E-G, Supplementary Fig. S1D). BRCA1-mutant HRD UWB cells were significantly more sensitive to the inhibitors than matched BRCA1-corrected HRP cells: ATRi VE-821 (LC50: 2.7-fold lower, p=0.05), CHK1i PF-477736 (LC50: 1.7-fold lower, p=0.01) and WEE1i MK-1775 (cell survival at 400 nM: 3.5-fold lower, p=0.05). However, BRCA2-mutated HRD V-C8 cells were no more sensitive to any of the checkpoint kinase inhibitors than their matched BRCA2-corrected HRP cells. Cells ranked in the same order of sensitivity for VE-821 and MK-1775 (most to least sensitive: UWB, C33A, UWB+B1, IGROV-1, V-C8, V-C8.B2, SiHa), but differed with PF-477736 (most to least sensitive: UWB, IGROV-1, UWB+B1, SiHa, V-C8, V-C8.B2, C33A). HPV negative C33A cells were more sensitive to VE-821 and MK-1775 compared to HPV positive SiHa cells, although C33A cells were the most resistant cell line to PF-477736. Concentrations (1 μM VE-821, 50 nM PF-477736 and 100 nM MK-1775) that were not excessively cytotoxic (cell kill <50% in HRP cells) across the panel of cells were selected for further study (Supplementary Fig. S1E).