Combined targeting of eIF4E and selinexor blocks tumor progression in vivo. Tet-on-sh-eIF4E U266 cells were subcutaneously injected into SCID/bg mice. (A) Subcutaneous tumor growth was measured using calipers and calculated with the following volume formula: 0.5 × long diameter × square of the short diameter. Each bar represents the mean ± SEM (n = 5). ∗P < .05. (B) Tumor volume was measured after 27 days. (C) Kaplan-Meier survival analysis of mice during 6 weeks of follow-up (n = 5 per group). Using a Log-Rank test, a survival benefit was observed for selinexor vs vehicle (P < .05) and selinexor + dox vs vehicle (P < .05). (D) Body weights were monitored every 3 days. No significant differences were observed between different groups. (E) Tumors harvested at the end of the study were fixed in 10% formalin and subsequently processed for immunohistochemical staining for eIF4E and IKZF1. The staining was observed using a Leica DMI 6000B microscope. Scale bar, 200 μM.