The dark matter of diffuse intrinsic pontine gliomas: an update

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.