Fig. 3: Trametinib and rapamycin combined treatment delays tumor formation and overall tumor load.

Cross-sectional histopathological analysis of tumor levels in liver (a,b), spleen (e,f) and kidney (i,j) samples of 24-month-old female mice (a,e,i) and male mice (b,f,j). Combined drug treatment significantly reduced liver tumors in both sexes at 24 months and spleen tumors in male mice, with a similar trend for reduced tumor load in female spleen and male and female kidney (e,f). The absence of liver tumors was scored with 0, and the presence of low, moderate, high and very high severity tumors was scored with 1, 2, 3 and 4, respectively. The absence or presence of spleen and kidney tumors was scored with 0 or 1, respectively. Liver tumor data for rapamycin and control animals were previously published²². Postmortem macropathology analysis of liver (c,d) and spleen (g,h) of animals from the lifespan and phenotyping cohort. k, Longitudinal analysis of spleen tumor progression via ¹⁸F-FDG PET/CT measurements in the same female animals at 12, 18 and 24 months of age. Although tumor load increased from 12 months to 24 months in control and trametinib-treated mice, combination-treated animals showed no increase. Data are presented as mean ± s.e.m. ¹⁸F-FDG uptake of rapamycin/trametinib versus control at 24 months P = 0.08. Two-way ANOVA with post hoc Bonferroni test and simple linear regression. (Control n = 7, trametinib n = 5 and rapamycin/trametinib n = 4). Data in a–j are presented as percentage over total, and statistical analysis was performed by two-sided chi-square test and Poisson regression. Numbers in brackets indicate the number of scored tissues per treatment.