Table 2.
Experimental pre-clinical therapeutics for pediatric high-grade gliomas including compound name, target of therapy, rationale for use in this disease, and references.
| Pre-Clinical Therapies for Pediatric High-Grade Gliomas | |||
|---|---|---|---|
| Compound(s) | Target | Rationale | Reference |
| VX-689 (renamed MK-5108) | AURKA (Aurora kinase A) |
Destabilizes MYC | [48] |
| MI-2 | MEN1 (Menin) |
Blocks menin-MLL-AF9 initiated leukemic oncogenesis; exact role in glioma undefined | [50,51] |
| GSK-J4 | JMJD3 (Jumonji-domain demethylase) |
Prevents further demethylation of H3K27 mark in H3-K27M mutated glioma | [52] |
| OTX-015 JQ1 |
BRD2/3/4 (Bromodomain-containing proteins) |
Interrupts BRD → H3-acetylation binding that is increased by H3.3-K27M | [53,54,55] |
| GSK126 GSK343 EPZ-6438 |
EZH2 (Enhancer of zeste homolog 2) |
De-represses tumor suppressor p16INK4a and induces apoptosis | [55,56,57] |
| BMS-754807 | Multi-kinase, most potent against IGF-1R (Insulin-like growth factor 1 receptor) |
Effective in compound screen; multiple valid targets in DIPG | [58] |
| PTC-209 | BMI-1 (polycomb group RING finger protein 4) |
Induces cell cycle arrest and telomerase downregulation, reduces migration, increases sensitivity to radiotherapy | [59,60] |