Diffuse intrinsic pontine glioma (DIPG): A review of current and emerging treatment strategies

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a childhood malignancy of the brainstem with a dismal prognosis. Despite recent advances in its understanding at the molecular level, the prognosis of DIPG has remained unchanged. This article aims to review the current understanding of the genetic pathophysiology of DIPG and to highlight promising therapeutic targets. Various DIPG treatment strategies have been investigated in pre-clinical studies, several of which have shown promise and have been subsequently translated into ongoing clinical trials. Ultimately, a multifaceted therapeutic approach that targets cell-intrinsic alterations, the micro-environment, and augments the immune system will likely be necessary to eradicate DIPG.

Figure 1:

H3 K27 mutation and subsequent tumorigenesis in DIPG. The H3 K27M mutation is a somatic gain-of-function missense mutation that results in lysine 27 to methionine substitution in histone 3 at either the H3.1 K27M (HIST1H3B gene mutation) or H3.3 K27M (H3F3A mutation) position. The H3 K27M mutation in a neural stem cell results in hypomethylation of the histone and gain of acetylation which is linked to downstream epigenetic and canonical oncogenic alterations which result in the development of DIPG. Listed are the key genes that contribute to the epigenetic and oncogenetic alterations of DIPG. Figure was created with the help of BioRender.com https://app.biorender.com.