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dc.contributor.authorLord, Simon R.
dc.contributor.authorCollins, Jennifer M.
dc.contributor.authorCheng, Wei-Chen
dc.contributor.authorHaider, Syed
dc.contributor.authorWigfield, Simon
dc.contributor.authorGaude, Edoardo
dc.contributor.authorFielding, Barbara A.
dc.contributor.authorPinnick, Katherine E.
dc.contributor.authorHarjes, Ulrike
dc.contributor.authorSegaran, Ashvina
dc.contributor.authorJha, Pooja
dc.contributor.authorHoefler, Gerald
dc.contributor.authorPollak, Michael N.
dc.contributor.authorThompson, Alastair M.
dc.contributor.authorRoy, Pankaj G.
dc.contributor.authorEnglish, Ruth.
dc.contributor.authorAdams, Rosie F.
dc.contributor.authorFrezza, Christian
dc.contributor.authorBuffa, Francesca M.
dc.contributor.authorKarpe, Fredrik
dc.contributor.authorHarris, Adrian L.
dc.date.accessioned2020-12-09T17:19:25Z
dc.date.available2020-12-09T17:19:25Z
dc.date.issued2019-12-10
dc.date.submitted2019-03-27
dc.identifier.issn0007-0920
dc.identifier.others41416-019-0665-5
dc.identifier.other665
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/314930
dc.descriptionFunder: Funder: Oxford NIHR Biomedical Research Centre. Grant reference number: A93195
dc.description.abstractAbstract: Background: Epidemiological studies suggest that metformin may reduce the incidence of cancer in patients with diabetes and multiple late phase clinical trials assessing the potential of repurposing this drug are underway. Transcriptomic profiling of tumour samples is an excellent tool to understand drug bioactivity, identify candidate biomarkers and assess for mechanisms of resistance to therapy. Methods: Thirty-six patients with untreated primary breast cancer were recruited to a window study and transcriptomic profiling of tumour samples carried out before and after metformin treatment. Results: Multiple genes that regulate fatty acid oxidation were upregulated at the transcriptomic level and there was a differential change in expression between two previously identified cohorts of patients with distinct metabolic responses. Increase in expression of a mitochondrial fatty oxidation gene composite signature correlated with change in a proliferation gene signature. In vitro assays showed that, in contrast to previous studies in models of normal cells, metformin reduces fatty acid oxidation with a subsequent accumulation of intracellular triglyceride, independent of AMPK activation. Conclusions: We propose that metformin at clinical doses targets fatty acid oxidation in cancer cells with implications for patient selection and drug combinations. Clinical Trial Registration: NCT01266486.
dc.languageen
dc.publisherNature Publishing Group UK
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectArticle
dc.subject/631/67/2327
dc.subject/631/67/1347
dc.subject/631/154/555
dc.subject/631/67/69
dc.subjectarticle
dc.titleTranscriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin
dc.typeArticle
dc.date.updated2020-12-09T17:19:24Z
prism.endingPage265
prism.issueIdentifier2
prism.publicationNameBritish Journal of Cancer
prism.startingPage258
prism.volume122
dc.identifier.doi10.17863/CAM.62039
dcterms.dateAccepted2019-11-12
rioxxterms.versionofrecord10.1038/s41416-019-0665-5
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidLord, Simon R. [0000-0001-7946-5609]
dc.contributor.orcidHarris, Adrian L. [0000-0003-1376-8409]
dc.identifier.eissn1532-1827
pubs.funder-project-idBreast Cancer Research Foundation (BCRF) (BCRF-18-064)
pubs.funder-project-idOxford University | Oxford Cancer Imaging Centre (OCIC) (C5255/A16466)
pubs.funder-project-idCancer Research UK (CRUK) (C602/A18974)


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