TABLE 1.
Preclinical studies targeting MB metabolism.
| Metabolic pathway | Drug | Application/Mechanism of action | References |
|---|---|---|---|
| Glycolysis | Oxamate (pyruvate analog) | Proliferation and motility impairment in MB cell lines through LDHA inhibition and increased OXPHOS. | Valvona and Fillmore, (2018) |
| Glycolysis | GSK 2837808A (LDHA/B inhibitor) | Reduced MB cell invasion | Qin et al. (2022) |
| Glycolysis | OSU03012 (PDK1 inhibitor) | Induction of mitochondrial-dependent apoptosis in vitro and in vivo MB models | Baryawno et al. (2010) |
| Glycolysis | 10058-F4 (MYC inhibitor) | Loss of SHH-induced HK2 upregulation in CGPCs by preventing MYC target genes expression | Gershon et al. (2013b) |
| Glutaminolysis | JHU395 | Apoptosis induction in MYC- expressing MB cell lines; Increased survival in MYC-amplified MB mouse models | Hanaford et al., 2019 |
| JHU-083 (prodrugs of glutamine analog 6-diazo-5-oxo-l-norleucine) | Pham et al. (2021) | ||
| Glutamine transporter SLC1A5 | None. Potentially druggable-target | non-WNT restricted MB. | Genovesi et al. (2021) |
| Inositol metabolism | Inositol hexakisphosphate (as single agent and combined with cisplatin) | Reduction of glycolysis and mTOR signaling; no OXPHOS activation in BMI1High; CHD7Low Group 4 MB cellular and in vivo models; enhanced IP6 cytotoxic effects in combination with cisplatin | Badodi et al. (2021) |
| Cholesterol biosynthesis | Simvastatin plus SMO antagonists (vismodegib or sonidegib) | Reduction of SHH MB cells proliferation and SHH-derived MB tumor growth in mice. Counteract SHH MB recurrence to SMO antagonist by inhibiting its cholesterol-mediated activation and SHH signaling | Gordon et al. (2018) |
| Fan et al. (2021) |