Fig. 5.

ATR inhibition alone is effective but not sufficient to achieve disease-free survival in a systemic primary B-ALL model. a IC₅₀ values of VE-822 in a panel of cancer cell lines and patient-derived samples (CellTiter-Glo assay at 72 h, mean ± s.d., n = 3). b, c Bioluminescence images b and quantification of whole-body radiance c of leukemia bearing mice treated with 40 mg kg^–1 VE-822 (n = 6) or vehicle (control, n = 6). VE-822 was administered once daily. d Kaplan-Meier survival analysis of C57BL/6 mice bearing p185^BCR-ABL Arf ^–/– systemic pre-B-ALL treated with 40 mg kg^–1 day^–1 VE-822 (n = 6) or vehicle (control, n = 6). Median survival for the control group was 15 days after treatment initiation and 32.5 days for the VE-822 group (Mantel–Cox test). e Apoptosis induction in p185^BCR-ABL Arf ^–/– pre-B-ALL cells treated as indicated (350 nM 3-AP, 100 nM VE-822, and 1 µM dCKi) for 72 h using flow cytometry for Annexin V and PI staining (mean ± s.d., n = 2, one-way analysis of variance, Bonferroni corrected). *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. HCC hepatocellular carcinoma, PDAC pancreatic ductal adenocarcinoma