Fig. 10: AKT and CDK9 co-inhibition recapitulates the effects of AKT and MCL1 co-inhibition in vivo.

A Individual tumour volumes of CP253c treated with ipatasertib (50 mg/kg; n = 5), fadraciclib (40 mg/kg; n = 6), combined treatment (n = 6) and vehicle (n = 5). B Predicted tumour growth using a linear mixed-effect model of CP253c treated with ipatasertib (50 mg/kg; n = 5), fadraciclib (40 mg/kg; n = 5), combined treatment (n = 5) and vehicle (n = 5). C Forest plots showing the results from the longitudinal mixed effect model for log-transformed tumour volume. Estimates and p-values refer to the interaction term of treatment arm and time indicating the difference in tumour volume growth rate between each treatment arm and the vehicle arm. Points represent the random effect coefficients for each drug group and error bars the 95% confidence intervals. The black dotted line indicates the vehicle (reference level). D Comparison of protein expression for cleaved caspase 3 (% positive cells), Ki67 (% positive cells) and pGSK3B, pPRAS40 and MCL1 H-score for the different treatment arms. Necrotic samples were not analysed. The box shows the interquartile range, the line indicates the mean, and the whiskers represent the minimum and maximum values. One-way ANOVA with post-hoc Fisher’s LSD test was performed. Representative IHC micrograph for end-of-treatment CP253c tumours are also shown (bottom panel). The scale bar indicates a length of 100 µm. Source data are provided as a Source Data file.