The dark matter of diffuse intrinsic pontine gliomas: an update

ABSTRACT

Introduction: DIPG represents the biggest therapeutic challenge in pediatric oncology and in neuro-oncology. Knowledge about its biology has dramatically increased in the last 5 years, but we are still missing efficient drugs for this unoperable tumor only transiently responding to radiotherapy.

Areas covered: Authors review the available recent literature describing the molecular and biological characteristics of this unique neoplasm. Therapeutic developement based on possible targets are described comprehensively. New areas for further therapeutic development are identified based on the mechanisms underlying the key phenotypic characteristics of these DIPG: epigenetic deregulation, chemo-radioresistance, and invasion.

Expert opinion: Barriers to the success of therapy are numerous but accretion of information is rapidly increasing. Epigenetic modifiers, alone or in combination represent the most promising approach at least in preclinical studies but their implementation in the clinic may need further refinement of either the way of administration of these drugs or the design of better brain penetrating and remaining drugs.

KEYWORDS:

• Diffuse midline glioma
• H3K27M mutant
• histone
• invasion
• radioresistance

Article highlights

• DIPG is an orphan disease with a unique oncogenesis.

• The hallmarks of the disease are epigenetic deregulation, chemo-radioresistance, and invasion but there is still a lot of dark matter to unravel in the biology of this disease.

• DIPG can be divided into subtypes based on their molecular landscape.

• No specific agent has reached a clinical validation and the disease is still orphan to medical treatment.

• The tumor cells are vulnerable to several epigenetic modifiers than should undergo clinical development alone or in combination.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by Etoile de Martin (2017 support) and Institut National du Cancer, France (PL BIO 14-253).