Fig. 7: Dual inhibition of FAO and AURKA extends animal survival in orthotopic patient-derived xenograft models of human GBM.

For a, b GBM12 cells were implanted into the subcutis of immunocompromised Nu/Nu mice. After the tumors were established, the mice were randomized to four treatment groups: vehicle, alisertib (30 mg/kg), etomoxir (20 mg/kg), and the combination treatment. The tumor volume over time is shown in (a) and the tumor volume on the last day of the experiment is shown in (b) (n = 8 in alisertib and etomoxir, n = 9 in vehicle and combination independent tumors) (*p = 0.0438, **p = 0.0085, ***p = 0.0003). For c, d GBM43 cells were implanted into the subcutis of immunocompromised Nu/Nu mice. After the tumors were established, the mice were randomized to four treatment groups: vehicle, alisertib (30 mg/kg), etomoxir (20 mg/kg), and combination treatment of both. The tumor volume over time is shown in (c) and the tumor volume on the last day of the experiment is shown in (d) (n = 9 in vehicle and etomoxir, n = 12 in alisertib and combination independent tumors) (Ali vs Combination: *p = 0.0462, etomoxir vs combination: *p = 0.0162). e GBM12 cells were implanted and treated with alisertib, etomoxir, or the combination of both as described in (a). On the last day of the experiment, mice were injected with 100 µM U-¹³C-palmitic acid for 4 h and tumors were subjected to LC/MS. The graph shows the U-¹³C-palmitic acid labeling of the TCA cycle. FC: fold change. f Tumors from the experiment in (a) were fixed and stained with PGC1α. Scale bar: 50 µM. For g, h GBM12 and GBM22 cells were implanted in the right striatum of nude mice. Four groups were randomly assigned: vehicle, alisertib, etomoxir, and combination of both, seven days after the implantation. Mice were treated three times per week and animal survival is provided (Kaplan−Meier-curve): vehicle: GBM12: 20d, GBM22: 20d; alisertib: GBM12: 28d, GBM22: 22d; etomoxir: GBM12: 25.5d, GBM22: 19.5d; combination: GBM12: 37.5d, GBM22: 26d. The log-rank test was used to assess statistical significance (n = 5 in vehicle and alisertib, n = 4 in etomoxir, n = 6 in combination). For (i−k) The brain tumors from the experiment in (h) were fixed and stained with H&E, TUNEL, or Ki67. Scale bar: 50 µm. l Quantification of TUNEL and Ki67 positive cells in (j, k), respectively (n = 5 in vehicle, etomoxir, combination, n = 6 in alisertib independent high-power field microscopy) (***p = 0.0001, ****p < 0.0001). Statistical significance was assessed by a two-tailed student’s t-test in e or ANOVA with Dunnett’s multiple comparison test in (b, d, l). Data are shown as mean ± SEM in (a, c) and as mean ± SD in (b, d, e, l). Source data are provided as a Source Data file.