{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:25:06Z","timestamp":1790717106126,"version":"4.1.0"},"reference-count":72,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2013brain 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\u2019 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-1\u03b1 and HIF-2\u03b1. 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.<\/jats:p>","DOI":"10.3390\/cancers12040979","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T05:15:41Z","timestamp":1587014141000},"page":"979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Hypoxia Inducible Factors\u2019 Signaling in Pediatric High-Grade Gliomas: Role, Modelization and Innovative Targeted Approaches"],"prefix":"10.3390","volume":"12","author":[{"given":"Quentin","family":"Fuchs","sequence":"first","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets team, Faculty of Pharmacy, 74 route du Rhin, 67405 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Pierrevelcin","sequence":"additional","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets team, Faculty of Pharmacy, 74 route du Rhin, 67405 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Messe","sequence":"additional","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets team, Faculty of Pharmacy, 74 route du Rhin, 67405 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Lhermitte","sequence":"additional","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets team, Faculty of Pharmacy, 74 route du Rhin, 67405 Illkirch, France"},{"name":"Pathology Department, University Hospital of Strasbourg, 1 avenue Moli\u00e8re, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Florence","family":"Blandin","sequence":"additional","affiliation":[{"name":"Pediatric Oncology, Dana Farber Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Papin","sequence":"additional","affiliation":[{"name":"Inserm U1258, UMR CNRS 7104, Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC), Universit\u00e9 de Strasbourg, 67400 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Coca","sequence":"additional","affiliation":[{"name":"Neurosurgery, University Hospital of Strasbourg, 1 avenue Moli\u00e8re, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Dontenwill","sequence":"additional","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets team, Faculty of Pharmacy, 74 route du Rhin, 67405 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natacha","family":"Entz-Werl\u00e9","sequence":"additional","affiliation":[{"name":"UMR CNRS 7021, Laboratory Bioimaging and Pathologies, Tumoral Signaling and Therapeutic Targets team, Faculty of Pharmacy, 74 route du Rhin, 67405 Illkirch, France"},{"name":"Pediatric Onco-Hematology Department, Pediatrics, University hospital of Strasbourg, 1 avenue Moli\u00e8re, 67098 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"x1","DOI":"10.1093\/neuonc\/nou327","article-title":"Alex\u2019s Lemonade Stand Foundation Infant and Childhood Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007\u20132011","volume":"16","author":"Ostrom","year":"2015","journal-title":"Neuro-Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.ccell.2017.08.017","article-title":"Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma","volume":"32","author":"Mackay","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s11060-019-03287-9","article-title":"Diagnostics and treatment of diffuse intrinsic pontine glioma: Where do we stand?","volume":"145","author":"Hendrikse","year":"2019","journal-title":"J. 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