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dc.contributor.authorFrentzas, S
dc.contributor.authorSimoneau, E
dc.contributor.authorBridgeman, VL
dc.contributor.authorVermeulen, PB
dc.contributor.authorFoo, S
dc.contributor.authorKostaras, E
dc.contributor.authorNathan, M
dc.contributor.authorWotherspoon, A
dc.contributor.authorGao, Z-H
dc.contributor.authorShi, Y
dc.contributor.authorVan den Eynden, G
dc.contributor.authorDaley, F
dc.contributor.authorPeckitt, C
dc.contributor.authorTan, X
dc.contributor.authorSalman, A
dc.contributor.authorLazaris, A
dc.contributor.authorGazinska, P
dc.contributor.authorBerg, TJ
dc.contributor.authorEltahir, Z
dc.contributor.authorRitsma, L
dc.contributor.authorVan Rheenen, J
dc.contributor.authorKhashper, A
dc.contributor.authorBrown, G
dc.contributor.authorNystrom, H
dc.contributor.authorSund, M
dc.contributor.authorVan Laere, S
dc.contributor.authorLoyer, E
dc.contributor.authorDirix, L
dc.contributor.authorCunningham, D
dc.contributor.authorMetrakos, P
dc.contributor.authorReynolds, AR
dc.date.accessioned2016-11-23T11:05:20Z
dc.date.issued2016-11
dc.identifier.citationNature medicine, 2016, 22 (11), pp. 1294 - 1302
dc.identifier.issn1078-8956
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/234
dc.identifier.eissn1546-170X
dc.identifier.doi10.1038/nm.4197
dc.description.abstractThe efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy.
dc.formatPrint-Electronic
dc.format.extent1294 - 1302
dc.languageeng
dc.language.isoeng
dc.subjectHT29 Cells
dc.subjectHumans
dc.subjectCarcinoma
dc.subjectCarcinoma, Ductal, Breast
dc.subjectCarcinoma, Lobular
dc.subjectBreast Neoplasms
dc.subjectColorectal Neoplasms
dc.subjectLiver Neoplasms
dc.subjectNeovascularization, Pathologic
dc.subjectAngiogenesis Inhibitors
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectCell Movement
dc.subjectDrug Resistance, Neoplasm
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectActin-Related Protein 2-3 Complex
dc.subjectGene Knockdown Techniques
dc.subjectNeoplasm Grading
dc.subjectBevacizumab
dc.titleVessel co-option mediates resistance to anti-angiogenic therapy in liver metastases.
dc.typeJournal Article
dcterms.dateAccepted2016-09-09
rioxxterms.versionofrecord10.1038/nm.4197
rioxxterms.licenseref.startdate2016-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature medicine
pubs.issue11
pubs.notes6 months
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Tumour Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Tumour Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume22
pubs.embargo.terms6 months
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamTumour Biologyen_US
icr.researchteamTranslational Immunotherapyen_US
dc.contributor.icrauthorReynolds, Andrewen
dc.contributor.icrauthorBridgeman, Victoriaen
dc.contributor.icrauthorFoo, Shaneen
dc.contributor.icrauthorNathan, Marken
dc.contributor.icrauthorDaley, Francesen
dc.contributor.icrauthorFrentzas, Sophiaen
dc.contributor.icrauthorCunningham, Daviden


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