Diffuse Intrinsic Pontine Glioma : Clinical Features, Molecular Genetics, and Novel Targeted Therapeutics

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative in vitro and preclinical models-using both xenografted material and genetically engineered mice-will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.

Keywords: Brainstem tumor; DIPG; Focused ultrasound; Glioma; Paediatric.

Fig. 1.

Magnetic resonance imaging (T2) showing lesion expanding the pons(white arrow), with associated signal change.

Fig. 2.

DIPG subgrouping map showing the current understanding between the interrelated DIPG subgroups (adapted from Misuraca et al. [41]). DIPG : diffuse intrinsic pontine glioma.

Fig. 3.

A : Magnetic resonance guided focused ultrasound preclinical system. B : Schematic of focused ultrasound (FUS) delivery causing temporary breach of blood-brain barrier within tumour. C : Schematic of FUS effect on microbubbles within blood vessel and resultant breach of BBB allowing delivery of gold nanoparticles (GNPs). MRI : magnetic resonance imaging , BBB : blood-brain barrier.