HSP90+MEK inhibitor combination therapy significantly extends survival. (A) Representative images of the changes in orthotopic tumor volumes in mice treated with vehicle or T/P combination therapy for 6 wk as recorded by HRUSI. Tumor outline is indicated by blue line. (B) Tumor volumes of mice bearing PDAC tumors treated with vehicle (“V”), trametinib (“T”, 2 mg/kg per day), PU-H71 (“P”, 75 mg/kg per day), or T/P for indicated times (mean ± SEM; n > 8 per group; *P < 0.05, **P < 0.01, ***P < 0.001; two-way ANOVA); (C) Kaplan–Meier survival curve of mice bearing PDAC tumors treated as described in AA (n > 8 per group; **P < 0.01; ***P < 0.001; log-rank test). (D–F(D–F) Quantification of proliferating Ki67/CK19+ cells (D), pERK+ cells (E), and dead/dying TUNEL+ cells (F) in PDAC tumors treated for 8 wk with vehicle or the T/P combination as described in AA (mean ± SEM; n = 5 per group; *P < 0.05, **P < 0.01; unpaired two-tailed t test). Representative immunohistochemical or immunofluorescence stainings are shown. (Scale bars, 50 µm.)