Fig. 4. Inhibition of CBP in CREBBP mutant tumors leads to radiosensitization in mutant but not wild-type in vivo HNSCC models.

a Individual tumor-growth curves in a UM-SCC-47 xenograft model expressing either control or two different CREBBP shRNAs following irradiation at 2 Gy/day for eight days. b Tumor-growth delay (to 500 mm3), tumor volume at collection, survival (all with n per group shown in panel a), and in vivo apoptosis (via TUNEL assay) (n = minimum of 4) in UM-SCC-47 xenograft tumors. Tumors for TUNEL assay were collected 8 h following the final dose of radiation in a concurrent experiment with tumor growth delay and survival. Log-rank statistics comparing shCREBBP-2 XRT or shCREBBP-3 XRT groups versus unirradiated control for each group were performed (two-sided p-value shown). c Individual growth curves, tumor-growth delay, and tumor volume at collection from a similar experiment performed in the UM-SCC-22a xenograft model. Of note, tumor-growth delay (n as shown in the tumor growth panel) to 350 mm³ was used for this experiment as many tumors in the treatment groups did not reach 500 mm³. d Individual growth curves, tumor-growth delay, and tumor volume at collection (n for both shown in the growth-curve panel) from a similar experiment in the Detroit 562 xenograft model. For bar graphs, data are presented as mean values +/− SEM. Significance tested via ANOVA with post hoc analysis adjusted for multiple comparisons. Two-sided p < 0.05 as indicated or compared with unirradiated shCREBBP (*), unirradiated control (+), irradiated control (#).