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Despite standard treatments such as surgical resection and chemoradiotherapy, overall survival (OS) usually does not exceed 14\u201316 months in clinical trials, and no improvement in OS has been demonstrated even with the use of vascular endothelial growth factor A (VEGFA) inhibitors such as bevacizumab. In response to radiotherapy, hypoxia-inducible factor (HIF) stabilization leads to activation of alternative pro-angiogenic pathways, increasing VEGF expression and tumor angiogenesis. Several clinical trials evaluating HIF-2\u03b1 inhibitors as monotherapy in the absence of concurrent VEGF inhibition, have similarly failed to demonstrate a significant improvement in OS outcomes. This review provides a perspective on the combined use of VEGF and HIF inhibitors, and provides an insight into future studies.<\/jats:p>","DOI":"10.1007\/s10495-026-02275-5","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T07:33:45Z","timestamp":1769153625000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enhancing the efficacy of VEGF inhibitors by co-inhibition of HIF in the treatment of glioblastoma"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9260-8316","authenticated-orcid":false,"given":"Emirhan","family":"Harbi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin Yozgat","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamza Ugur","family":"Bozbey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didem","family":"Tastekin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oral","family":"Oncul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soha","family":"Hosseiny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duha","family":"Yahya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozcan","family":"Yildiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Erdogan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Kadir","family":"Slocum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Aschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"2275_CR1","doi-asserted-by":"crossref","unstructured":"Sharma P, Aaroe A, Liang J, Puduvalli VK (2023) Tumor microenvironment in glioblastoma: Current and emerging concepts. 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