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Drug Resist Updat. 2019 Jun 7;44:15-25. doi: 10.1016/j.drup.2019.06.001. [Epub ahead of print]

Preclinical therapeutic targets in diffuse midline glioma.

Author information

1
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, Cancer Center Amsterdam, the Netherlands.
2
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, Cancer Center Amsterdam, the Netherlands. Electronic address: e.hulleman@prinsesmaximacentrum.nl.

Abstract

Diffuse midline gliomas (DMG) are rapidly fatal tumors of the midbrain in children, characterized by a diffuse growing pattern and high levels of intrinsic resistance to therapy. The location of these tumors, residing behind the blood-brain barrier (BBB), and the limited knowledge about the biology of these tumors, has hindered the development of effective treatment strategies. However, the introduction of diagnostic biopsies and the implementation of autopsy protocols in several large centers world-wide has allowed for a detailed characterization of these rare tumors. This has resulted in the identification of novel therapeutic targets, as well as major advances in understanding the biology of DMG in relation to therapy resistance. We here provide an overview of the cellular pathways and tumor-specific aberrations that have been targeted in preclinical DMG research, and discuss the advantages and limitations of these therapeutic strategies in relation to therapy resistance and BBB-penetration. Therewith, we aim to provide researchers with a framework for successful preclinical therapy development.

KEYWORDS:

Anticancer drug resistance; Blood-brain barrier; Diffuse midline glioma; Pediatric high grade glioma; Preclinical therapy development; Targeted therapy

PMID:
31202081
DOI:
10.1016/j.drup.2019.06.001

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