Skip to main content
. 2022 Mar 15;82(6):1140–1152. doi: 10.1158/0008-5472.CAN-21-2997

Figure 2.

Figure 2. Antitumor in vivo efficacy of AZD6738 across multiple ATM-deficient cell line xenograft models. A and B, LoVo (MRE11A), Granta-519, NCI-H23, 549 (ATM-proficient control; A) and FaDu ATM knockout (B). AZD6738 was dosed at the indicated duration and doses either once daily (qd) or twice daily (bid). Mean tumor volume ± SEM is shown. C, LoVo xenograft IHC pharmacodynamics for CHK1 Ser345, γH2AX, and pRAD50 Ser645 biomarkers. AZD6738 was dosed at the indicated doses once daily for 3 to 4 days and tumor harvested at time 0 (day 4, before the 4th dose) or 2, 8, or 24 hours after fourth daily dose. Mean percentage of positive staining nuclei plus SD is shown. D, Change in expression for each biomarker. E, Free plasma AUC versus %TGI for each biomarker at 8 hours. F, AZD6738 dose versus %TGI for each biomarker at 8 hours. ns, nonsignificant; **, P ≤ 0.01; ***, P ≤ 0.001.

Antitumor in vivo efficacy of AZD6738 across multiple ATM-deficient cell line xenograft models. A and B, LoVo (MRE11A), Granta-519, NCI-H23, 549 (ATM-proficient control; A) and FaDu ATM knockout (B). AZD6738 was dosed at the indicated duration and doses either once daily (qd) or twice daily (bid). Mean tumor volume ± SEM is shown. C, LoVo xenograft IHC pharmacodynamics for CHK1 Ser345, γH2AX, and pRAD50 Ser645 biomarkers. AZD6738 was dosed at the indicated doses once daily for 3 to 4 days and tumor harvested at time 0 (day 4, before the 4th dose) or 2, 8, or 24 hours after fourth daily dose. Mean percentage of positive staining nuclei plus SD is shown. D, Change in expression for each biomarker. E, Free plasma AUC versus %TGI for each biomarker at 8 hours. F, AZD6738 dose versus %TGI for each biomarker at 8 hours. ns, nonsignificant; **, P ≤ 0.01; ***, P ≤ 0.001.