Fig. 4.
NAMPT inhibitors are effective in vivo agents against PPM1D mutant xenografts. a Fold change in tumor growth for serially-transplanted PPM1Dtrnc. xenografts in NSG mice treated with vehicle or 20 mg/kg FK866 BID for 3 cycles of: 4 days on, followed by 3 days off (n = 7 animals, ***p < 0.001 by Mann–Whitney U test, error bars represent standard deviation of the mean). Arrows indicate initiation of treatment cycle. b Kaplan–Meier plot of xenograft tumor growth from (a), with arrows indicating initiation of treatment cycle (p < 0.0001 by Log rank (Mantel-Cox) test). c NAPRT expression levels for PNOC003 DIPG cohort31 samples. d Model depicting the mechanism of mutant PPM1D-induced dependence on NAMPT for NAD production, and synthetic lethality with NAMPT inhibitors, such as FK866