Treatment with CCNU + 9-ING-41 leads to regression of TMZ-resistant intracranial GBM12 tumors. (A) Mice were staged and randomized based on BLI. Mice were treated (red arrow) daily, Monday to Friday, with TMZ (n = 5; 50 mg/kg, oral administration) or TMZ + 9-ING-41 (n = 5; 40 mg/kg of 9-ING-41, i.p.) for 1 week. The treatment was continued (purple arrow) with CCNU (5 mg/kg, i.p., TMZ-treated group) and CCNU + 9-ING-41 (TMZ + 9-ING-41-treated group) twice a week for 4 weeks. (B) Kaplan-Meier survival analysis of GBM12-bearing mice treated as described in panel A. The median survival in the CCNU group was 87 days. Four of five CCNU + 9-ING-41–treated animals were intentionally euthanized (censored) for histological analysis of brain at day 130 despite being healthy and luciferase-signal free. Combination of CCNU and 9-ING-41 significantly prolonged survival of animals as compared to CCNU-treated group (P < .05).