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dc.contributor.authorBaker, LCJ
dc.contributor.authorSikka, A
dc.contributor.authorPrice, JM
dc.contributor.authorBoult, JKR
dc.contributor.authorLepicard, EY
dc.contributor.authorBox, G
dc.contributor.authorJamin, Y
dc.contributor.authorSpinks, TJ
dc.contributor.authorKramer-Marek, G
dc.contributor.authorLeach, MO
dc.contributor.authorEccles, SA
dc.contributor.authorBox, C
dc.contributor.authorRobinson, SP
dc.date.accessioned2018-08-14T10:24:23Z
dc.date.issued2018-07-23
dc.identifier.citationFrontiers in oncology, 2018, 8 pp. 271 - ?
dc.identifier.issn2234-943X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2332
dc.identifier.eissn2234-943X
dc.identifier.doi10.3389/fonc.2018.00271
dc.description.abstractBackground: Overexpression of EGFR is a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). Patients with HNSCC who respond to EGFR-targeted tyrosine kinase inhibitors (TKIs) eventually develop acquired resistance. Strategies to identify HNSCC patients likely to benefit from EGFR-targeted therapies, together with biomarkers of treatment response, would have clinical value. Methods: Functional MRI and 18F-FDG PET were used to visualize and quantify imaging biomarkers associated with drug response within size-matched EGFR TKI-resistant CAL 27 (CALR) and sensitive (CALS) HNSCC xenografts in vivo, and pathological correlates sought. Results: Intrinsic susceptibility, oxygen-enhanced and dynamic contrast-enhanced MRI revealed significantly slower baseline R2∗ , lower hyperoxia-induced ΔR2∗ and volume transfer constant Ktrans in the CALR tumors which were associated with significantly lower Hoechst 33342 uptake and greater pimonidazole-adduct formation. There was no difference in oxygen-induced ΔR1 or water diffusivity between the CALR and CALS xenografts. PET revealed significantly higher relative uptake of 18F-FDG in the CALR cohort, which was associated with significantly greater Glut-1 expression. Conclusions: CALR xenografts established from HNSCC cells resistant to EGFR TKIs are more hypoxic, poorly perfused and glycolytic than sensitive CALS tumors. MRI combined with PET can be used to non-invasively assess HNSCC response/resistance to EGFR inhibition.
dc.formatElectronic-eCollection
dc.format.extent271 - ?
dc.languageeng
dc.language.isoeng
dc.publisherFRONTIERS MEDIA SA
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleEvaluating Imaging Biomarkers of Acquired Resistance to Targeted EGFR Therapy in Xenograft Models of Human Head and Neck Squamous Cell Carcinoma.
dc.typeJournal Article
dcterms.dateAccepted2018-07-02
rioxxterms.versionofrecord10.3389/fonc.2018.00271
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfFrontiers in oncology
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Preclinical Molecular Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Preclinical Molecular Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radiotherapy Physics Modelling
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Preclinical Molecular Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Magnetic Resonance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Preclinical Molecular Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radiotherapy Physics Modelling
pubs.publication-statusPublished
pubs.volume8
pubs.embargo.termsNot known
icr.researchteamMagnetic Resonance
icr.researchteamPreclinical Molecular Imaging
icr.researchteamPre-Clinical MRI
icr.researchteamRadiotherapy Physics Modelling
dc.contributor.icrauthorPrice, Jonathan
dc.contributor.icrauthorBoult, Jessica
dc.contributor.icrauthorLepicard, Elise
dc.contributor.icrauthorJamin, Yann
dc.contributor.icrauthorKramer-Marek, Gabriela
dc.contributor.icrauthorLeach, Martin
dc.contributor.icrauthorBox, Carol
dc.contributor.icrauthorRobinson, Simon


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