J Korean Neurosurg Soc.  2018 May;61(3):343-351. 10.3340/jkns.2018.0008.

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

• Mathew RK
• Rutka JT

• KMID: 2417359
• DOI: http://doi.org/10.3340/jkns.2018.0008

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.

Keyword

Glioma; Paediatric; DIPG; Brainstem tumor; Focused ultrasound

MeSH Terms

Biology
Brain Neoplasms
Brain Stem Neoplasms
Carcinogenesis
Glioma*
Heterografts
Histones
Hope
In Vitro Techniques
Methylation
Molecular Biology*
Prognosis
Histones

Figure

• 

  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.

Reference

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