Figure 4.

Imatinib increases radiotherapy-induced tumor growth delay without increasing intestinal toxicity in a PC-3 prostate cancer xenograft. (A) Intestinal crypt cell survival in BALB/c mice following 1–18 Gy in vivo in the presence of 50 mg/kg/d for 5 d. Surviving crypts were scored 3 d after irradiation based on three mice per treatment group. Points, mean survival; bars, SD. Inset, H&E-stained section of intestinal crypts before and after 14 Gy. (B) Plot of growth delay of PC3 xenografts treated with PBS alone, imatinib (50 mg/kg/d × 8 d) alone, 4 Gy × 5 plus PBS, or 4 Gy × 5 plus imatinib. Irradiated mice were either pretreated with 3 d PBS (sham) or 3 d imatinib (50 mg/kg/d i.p.) before irradiation and received daily PBS or imatinib i.p. dosing during 4 Gy daily radiation fractions for a total treatment period of 8 d similar to drug alone. For clarity, the median animal per group is shown. The calculated mean growth delay based on 9–10 mice per group was 100 ± 7 d for the combined treatment group, compared with 74 ± 14 d for the radiotherapy alone group (p = 0.003). There was no difference in growth delay between the imatinib alone and control groups. (Adapted and reprinted with permission from the American Association for Cancer Research: Choudhury et al., “Targeting homologous recombination using imatinib results in enhanced tumor cell chemosensitivity and radiosensitivity,” Mol Cancer Ther 2009; 8:203–13).