K14E6/E7 mice were given no treatment (Control), topical BEZ235 alone (Topical BEZ235), DMBA alone (DMBA), or DMBA and topical BEZ235 concurrently (DMBA+ Topical BEZ235). To evaluate the on-target effect of topical BEZ235 treatment, fixed tissue sections were stained for pAkt and pS6 using immunohistochemistry. Compared to mice treated with DMBA alone, panel A shows the addition of topical BEZ235 treatment to DMBA significantly decreased pAkt protein expression (mean ± SEM; 0.159 ± 0.008 vs 0.119 ± 0.002; *P = 0.00023). In panel B, the addition of topical BEZ235 treatment to DMBA treatment significantly decreased pS6 compared to DMBA controls (mean ± SEM; 0.115 ± 0.002 vs 0.142 ± 0.004; *P = 0.000014).