(A) Schematic illustrating the experimental design. Athymic nude mice were treated with a single dose of QST (10 mg/kg) through IP injection, SC injection, or OG. Blood samples were collected at 0.5, 1, 2, 4, 6, 8, and 24 hours after dosing and analyzed by LC-MS/MS. (B) Total plasma concentration–time curve for QST administered through various routes. Values for AUC_last were calculated for each route to illustrate plasma QST exposure (bottom). Error bars indicate SEM. (C) Schematic illustrating the treatment regimen for mice with flank tumors. When the tumors reached a mean volume of 100 mm³, mice were randomized into 4 groups: vehicle, 10 mg/kg QST, IR alone (6 Gy), or combination treatment (6 Gy IR and 10 mg/kg QST) (n = 10 mice in each cohort). IR was given in fractionated doses (2 Gy MWF) only during the first week of treatment, with or without QST. Following completion of IR, mice in the monotherapy and combination cohorts continued to receive QST alone on MWF until the tumors reached the indicated volume threshold. (D) Weekly mean volume measurements of U87 flank tumors from mice treated with vehicle, QST, IR, or a combination of QST and IR (QST+IR) (n = 10 mice in each cohort). Error bars indicate SEM. (E) Mean weights of mice from each cohort throughout the study duration. Error bars indicate SEM. (F) Total levels of QST in plasma and flank tumors of mice treated with QST and QST+IR (n = 3 or 4 mice per cohort). Error bars indicate SEM. (G) Immunoblotting of protein lysate–derived homogenized flank tumors from each cohort (n = 3 mice per group). Membranes were probed for H3K9/14ac, H3K27ac, γ-H2AX, and β-actin. Differences were assessed using ordinary 1-way ANOVA with Dunnett’s multiple-comparison test.