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Hypoxia Inducible Factors’ Signaling in Pediatric High-Grade Gliomas: Role, Modelization and Innovative Targeted Approaches

1
UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets team, Faculty of Pharmacy, 74 route du Rhin, 67405 Illkirch, France
2
Pathology Department, University Hospital of Strasbourg, 1 avenue Molière, 67098 Strasbourg, France
3
Pediatric Oncology, Dana Farber Institute, Boston, MA 02215, USA
4
Inserm U1258, UMR CNRS 7104, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, 67400 Illkirch, France
5
Neurosurgery, University Hospital of Strasbourg, 1 avenue Molière, 67098 Strasbourg, France
6
Pediatric Onco-Hematology Department, Pediatrics, University hospital of Strasbourg, 1 avenue Molière, 67098 Strasbourg, France
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(4), 979; https://doi.org/10.3390/cancers12040979
Received: 4 March 2020 / Revised: 4 April 2020 / Accepted: 7 April 2020 / Published: 15 April 2020
(This article belongs to the Special Issue Inhibition of HIFs as an Anti-Cancer Strategy)
The brain tumor microenvironment has recently become a major challenge in all pediatric cancers, but especially in brain tumors like high-grade gliomas. Hypoxia is one of the extrinsic tumor features that interacts with tumor cells, but also with the blood–brain barrier and all normal brain cells. It is the result of a dramatic proliferation and expansion of tumor cells that deprive the tissues of oxygen inflow. However, cancer cells, especially tumor stem cells, can endure extreme hypoxic conditions by rescheduling various genes’ expression involved in cell proliferation, metabolism and angiogenesis and thus, promote tumor expansion, therapeutic resistance and metabolic adaptation. This cellular adaptation implies Hypoxia-Inducible Factors (HIF), namely HIF-1α and HIF-2α. In pediatric high-grade gliomas (pHGGs), several questions remained open on hypoxia-specific role in normal brain during gliomagenesis and pHGG progression, as well how to model it in preclinical studies and how it might be counteracted with targeted therapies. Therefore, this review aims to gather various data about this key extrinsic tumor factor in pHGGs. View Full-Text
Keywords: high-grade gliomas; pediatric; hypoxia; HIFs high-grade gliomas; pediatric; hypoxia; HIFs
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Fuchs, Q.; Pierrevelcin, M.; Messe, M.; Lhermitte, B.; Blandin, A.-F.; Papin, C.; Coca, A.; Dontenwill, M.; Entz-Werlé, N. Hypoxia Inducible Factors’ Signaling in Pediatric High-Grade Gliomas: Role, Modelization and Innovative Targeted Approaches. Cancers 2020, 12, 979.

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