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dc.contributor.authorLord, SR
dc.contributor.authorCollins, JM
dc.contributor.authorCheng, W-C
dc.contributor.authorHaider, S
dc.contributor.authorWigfield, S
dc.contributor.authorGaude, E
dc.contributor.authorFielding, BA
dc.contributor.authorPinnick, KE
dc.contributor.authorHarjes, U
dc.contributor.authorSegaran, A
dc.contributor.authorJha, P
dc.contributor.authorHoefler, G
dc.contributor.authorPollak, MN
dc.contributor.authorThompson, AM
dc.contributor.authorRoy, PG
dc.contributor.authorEnglish, R
dc.contributor.authorAdams, RF
dc.contributor.authorFrezza, C
dc.contributor.authorBuffa, FM
dc.contributor.authorKarpe, F
dc.contributor.authorHarris, AL
dc.date.accessioned2021-06-11T11:38:05Z
dc.date.available2021-06-11T11:38:05Z
dc.identifier.citationBritish journal of cancer, 2020, 122 (2), pp. 258 - 265
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4618
dc.identifier.eissn1532-1827
dc.identifier.eissn1532-1827en_US
dc.identifier.doi10.1038/s41416-019-0665-5
dc.identifier.doi10.1038/s41416-019-0665-5en_US
dc.description.abstractBackground 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.formatPrint-Electronic
dc.format.extent258 - 265
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectMitochondria
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectBreast Neoplasms
dc.subjectDiabetes Mellitus
dc.subjectMetformin
dc.subjectProtein Kinases
dc.subjectFatty Acids
dc.subjectGene Expression Profiling
dc.subjectCell Proliferation
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectOxidation-Reduction
dc.subjectLipid Peroxidation
dc.subjectFemale
dc.subjectLipid Metabolism
dc.subjectTranscriptome
dc.subjectHeterografts
dc.titleTranscriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin.
dc.typeJournal Article
dcterms.dateAccepted2019-11-12
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1038/s41416-019-0665-5
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
dc.relation.isPartOfBritish journal of cancer
pubs.issue2
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume122en_US
pubs.embargo.termsNot known
dc.contributor.icrauthorHaider, Syeden


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