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dc.contributor.authorLee, Shen-Han
dc.contributor.authorGolinska, Monika
dc.contributor.authorGriffiths, John
dc.date.accessioned2021-11-25T17:28:56Z
dc.date.available2021-11-25T17:28:56Z
dc.date.issued2021-09-09
dc.identifier.issn2073-4409
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331181
dc.description.abstractIn solid tumours, cancer cells exist within hypoxic microenvironments, and their metabolic adaptation to this hypoxia is driven by HIF-1 transcription factor, which is overexpressed in a broad range of human cancers. HIF inhibitors are under pre-clinical investigation and clinical trials, but there is evidence that hypoxic cancer cells can adapt metabolically to HIF-1 inhibition, which would provide a potential route for drug resistance. Here, we review accumulating evidence of such adaptions in carbohydrate and creatine metabolism and other HIF-1-independent mechanisms that might allow cancers to survive hypoxia despite anti-HIF-1 therapy. These include pathways in glucose, glutamine, and lipid metabolism; epigenetic mechanisms; post-translational protein modifications; spatial reorganization of enzymes; signalling pathways such as Myc, PI3K-Akt, 2-hyxdroxyglutarate and AMP-activated protein kinase (AMPK); and activation of the HIF-2 pathway. All of these should be investigated in future work on hypoxia bypass mechanisms in anti-HIF-1 cancer therapy. In principle, agents targeted toward HIF-1β rather than HIF-1α might be advantageous, as both HIF-1 and HIF-2 require HIF-1β for activation. However, HIF-1β is also the aryl hydrocarbon nuclear transporter (ARNT), which has functions in many tissues, so off-target effects should be expected. In general, cancer therapy by HIF inhibition will need careful attention to potential resistance mechanisms.
dc.format.mediumElectronic
dc.languageeng
dc.publisherMDPI AG
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleHIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells.
dc.typeArticle
prism.issueIdentifier9
prism.publicationDate2021
prism.publicationNameCells
prism.volume10
dc.identifier.doi10.17863/CAM.78628
dc.identifier.doi10.17863/CAM.78628
dcterms.dateAccepted2021-09-02
rioxxterms.versionofrecord10.3390/cells10092371
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-09-09
dc.contributor.orcidLee, Shen-Han [0000-0002-6147-2963]
dc.contributor.orcidGriffiths, John [0000-0001-7369-6836]
dc.identifier.eissn2073-4409
rioxxterms.typeJournal Article/Review
cam.issuedOnline2021-09-09


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International