{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:08:39Z","timestamp":1791284919056,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the realm of cancer therapeutics, targeting the hypoxia-inducible factor (HIF) pathway has emerged as a promising strategy. This study delves into the intricate web of HIF-associated mechanisms, exploring avenues for future anticancer therapies. Framing the investigation within the broader context of cancer progression and hypoxia response, this article aims to decipher the pivotal role played by HIF in regulating genes influencing angiogenesis, cell proliferation, and glucose metabolism. Employing diverse approaches such as HIF inhibitors, anti-angiogenic therapies, and hypoxia-activated prodrugs, the research methodologically intervenes at different nodes of the HIF pathway. Findings showcase the efficacy of agents like EZN-2968, Minnelide, and Acriflavine in modulating HIF-1\u03b1 protein synthesis and destabilizing HIF-1, providing preliminary proof of HIF-1\u03b1 mRNA modulation and antitumor activity. However, challenges, including toxicity, necessitate continued exploration and development, as exemplified by ongoing clinical trials. This article concludes by emphasizing the potential of targeted HIF therapies in disrupting cancer-related signaling pathways.<\/jats:p>","DOI":"10.3390\/ijms25042060","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T03:36:17Z","timestamp":1707363377000},"page":"2060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Therapeutic Targeting of Hypoxia-Inducible Factors in Cancer"],"prefix":"10.3390","volume":"25","author":[{"given":"Saba","family":"Musleh Ud Din","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Memorial Healthcare System, 703 North Flamingo Road, Pembroke Pines, FL 33028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer G.","family":"Streit","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Memorial Healthcare System, 703 North Flamingo Road, Pembroke Pines, FL 33028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao Tran","family":"Huynh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Memorial Healthcare System, 703 North Flamingo Road, Pembroke Pines, FL 33028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6663-3535","authenticated-orcid":false,"given":"Caroline","family":"Hana","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Memorial Healthcare System, 703 North Flamingo Road, Pembroke Pines, FL 33028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Ninny","family":"Abraham","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Memorial Healthcare System, 703 North Flamingo Road, Pembroke Pines, FL 33028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atif","family":"Hussein","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Memorial Healthcare System, 703 North Flamingo Road, Pembroke Pines, FL 33028, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,8]]},"reference":[{"key":"ref_1","first-page":"85","article-title":"Global burden of cancer","volume":"79","author":"Ma","year":"2006","journal-title":"Yale J. 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