Fig. 5: OT-82 impairs tumor growth and prolongs survival in EWS orthotopic xenograft models.

a EWS xenograft tumor volumes on days 15 (TC71) and 18 (TC32) after treatment with vehicle or OT-82 at 5, 25, or 50 mg/kg. Animals (n = 5/group) were dosed with OT-82 on days 0–2, 7–9, 14–16, and 21–24. Double asterisks (**) denote p < 0.01, quadruple asterisks (****) denote p < 0.0001. b Corresponding Kaplan–Meier curves representing survival to endpoint (17 mm in longest tumor diameter) for mice bearing EWS xenograft tumors and treated with vehicle or 5, 25, or 50 mg/kg OT-82 as described in a. Black arrows represent treatment schedule; red arrows represent final day of treatment. In TC71 xenografts, p = 0.0093 for 25 mg/kg compared to control and p = 0.0050 for 50 mg/kg compared to control; in TC32 xenografts, p < 0.0001 for both 25 mg/kg and 50 mg/kg compared to control, using Mantel–Cox analysis. c Total NAD concentration in EWS xenograft tumors (n = 3 mice/condition) treated with vehicle or OT-82 at 5, 25 or 50 mg/kg for 3 days. Tumors were harvested 2 h after third dose. Double asterisks (**) denote p < 0.01, single asterisk (*) denotes p < 0.05. d PAR activity in EWS xenograft tumors (n = 3 mice/condition) treated with vehicle or 50 mg/kg OT-82 for 3 days. Tumors were harvested 2 h after third dose. Single asterisk (*) denotes p < 0.05.