{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:45:57Z","timestamp":1792626357533,"version":"4.5.0"},"reference-count":139,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CM19\/00068"],"award-info":[{"award-number":["CM19\/00068"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glioblastoma is the most aggressive form of brain tumor in adults and is characterized by the presence of hypervascularization and necrosis, both caused by a hypoxic microenvironment. In this review, we highlight that hypoxia-induced factor 1 (HIF-1), the main factor activated by hypoxia, is an important driver of tumor progression in GB patients. HIF-1\u03b1 is a transcription factor regulated by the presence or absence of O2. The expression of HIF-1 has been related to high-grade gliomas and aggressive tumor behavior. HIF-1 promotes tumor progression via the activation of angiogenesis, immunosuppression, and metabolic reprogramming, promoting cell invasion and survival. Moreover, in GB, HIF-1 is not solely modulated by oxygen but also by oncogenic signaling pathways, such as MAPK\/ERK, p53, and PI3K\/PTEN. Therefore, the inhibition of the hypoxia pathway could represent an important treatment alternative in a disease with very few therapy options. Here, we review the roles of HIF-1 in GB progression and the inhibitors that have been studied thus far, with the aim of shedding light on this devastating disease.<\/jats:p>","DOI":"10.3390\/ijms222212608","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T04:48:37Z","timestamp":1638247717000},"page":"12608","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":177,"title":["Hypoxia: The Cornerstone of Glioblastoma"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4827-9170","authenticated-orcid":false,"given":"Marta","family":"Dom\u00e8nech","sequence":"first","affiliation":[{"name":"B\u00b7ARGO (Badalona Applied Research Group of Oncology) Medical Oncology Department, Catalan Institute of Oncology Badalona, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ainhoa","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"B\u00b7ARGO (Badalona Applied Research Group of Oncology) Medical Oncology Department, Catalan Institute of Oncology Badalona, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7862-9197","authenticated-orcid":false,"given":"Andrea","family":"Plaja","sequence":"additional","affiliation":[{"name":"B\u00b7ARGO (Badalona Applied Research Group of Oncology) Medical Oncology Department, Catalan Institute of Oncology Badalona, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4501-7100","authenticated-orcid":false,"given":"Eva","family":"Mart\u00ednez-Balibrea","sequence":"additional","affiliation":[{"name":"Germans Trias i Pujol Research Institute (IGTP), ProCURE Program, Catalan Institute of Oncology, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0771-0390","authenticated-orcid":false,"given":"Carmen","family":"Bala\u00f1\u00e0","sequence":"additional","affiliation":[{"name":"B\u00b7ARGO (Badalona Applied Research Group of Oncology) Medical Oncology Department, Catalan Institute of Oncology Badalona, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"2005STUPP rt + tmz","volume":"352","author":"Stupp","year":"2005","journal-title":"N. 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