Potential New Therapies for Pediatric Diffuse Intrinsic Pontine Glioma

Abstract

Diffuse intrinsic pontine glioma (DIPG) is an extensively invasive malignancy with infiltration into other regions of the brainstem. Although large numbers of specific targeted therapies have been tested, no significant progress has been made in treating these high-grade gliomas. Therefore, the identification of new therapeutic approaches is of great importance for the development of more effective treatments. This article reviews the conventional therapies and new potential therapeutic approaches for DIPG, including epigenetic therapy, immunotherapy, and the combination of stem cells with nanoparticle delivery systems.

Keywords: DIPG; H3K27M; epigenetic therapy; immunotherapy; nanoparticles; stem cells.

FIGURE 1

Genetic and epigenetic alterations found in DIPG. Red boxes indicate mutations.

FIGURE 2

Schematic illustration of potential epigenetic therapies for DIPG. Histone methylase and demethylase inhibitors, histone deacetylase inhibitors, BET protein inhibitors and DNA methylation inhibitors may all serve as potential therapeutic targets suppressing tumorigenesis of H3K27M DIPGs.

FIGURE 3

Schematic overview of current immunotherapeutic strategies in DIPG. Multiple immunotherapy methods that are undergoing clinical trials in DIPG, including an EGFRvIII peptide vaccine, a B7-H3 vaccine and anti-PD-1 immune checkpoint inhibitors, are depicted.

FIGURE 4

Combination of genetically engineered stem cells and nanotechnology in the treatment of DIPG. The glioma cells-homing behavior of neural stem cells (NSCs) and mesenchymal stem cells (MSCs) was utilized to deliver nanoparticles carrying drugs to DIPG tumor.