(A) Kaplan-Meier survival curves of 2153L tumor–bearing mice from treatment start time. (B) Survival regression analysis of 2153L tumor–bearing mice. Survival data were fitted using a parametric survival regression model with a log-normal distribution. The top table reports all possible pairwise comparisons using linear contrasts that are adjusted for multiple comparisons using Holm’s method. The bottom table tests for overall main effects and interactions. In A and B, data from 3 to 5 independent experimental batches are integrated. n = 24 for vehicle, n = 22 for zotatifin, n = 13 for carboplatin, and n = 24 for zotatifin + carboplatin. (C and D) Kaplan-Meier survival curves of 2225L-LM2 (C) or 2208L (D) tumor–bearing mice from treatment start time. Mice were randomized and treatment was initiated when 2225L-LM2 tumors reached approximately 130 mm³ volume or 2208L tumors reached approximately 210 mm³ volume. n = 5 biological replicates per group. (E) Left: Representative images of IF staining of γH2A.X (in red) in 2153L tumors that were treated with indicated drugs for 3 days. Scale bars: 50 μm. Right, quantification of IF staining. At least 2 representative views were analyzed for each tumor and at least 3 tumors for each treatment group were analyzed. Data are presented as mean ± SEM and were analyzed using 2-tailed, unpaired Student’s t test. (F) Kaplan-Meier survival curves of 2153L tumor–bearing mice treated with indicated drugs. n ≥ 4 biological replicates per group. (G) Kaplan-Meier survival curves of 2225L-LM2 tumor–bearing mice treated with indicated drugs. n ≥ 3 biological replicates per group. (H) Kaplan-Meier survival curves of 2208L tumor–bearing mice treated with indicated drugs. n = 4 biological replicates per group. In C, D, and F–H, the log-rank test (2-tailed) was used to test for the significant differences of curves between groups.