Synergistic anti-tumor efficacy of mutant isocitrate dehydrogenase 1 inhibitor SYC-435 with standard therapy in patient-derived xenograft mouse models of glioma

•A novel pair of orthotopic PDX models of glioma bearing IDH1-R132H/R132C mutations.•New mutant IDH1i (SY-435) with standard therapy led to strong therapeutic efficacy.•H3K4/K9 methylation/mtDNA-encoded molecules mediate anti-tumor activity of SYC-435.•Discovered MYO1F, CTC1 and BCL9 as novel genes that mediated SYC-435 resistance.