dc.contributor.author | Frentzas, S | |
dc.contributor.author | Simoneau, E | |
dc.contributor.author | Bridgeman, VL | |
dc.contributor.author | Vermeulen, PB | |
dc.contributor.author | Foo, S | |
dc.contributor.author | Kostaras, E | |
dc.contributor.author | Nathan, M | |
dc.contributor.author | Wotherspoon, A | |
dc.contributor.author | Gao, Z-H | |
dc.contributor.author | Shi, Y | |
dc.contributor.author | Van den Eynden, G | |
dc.contributor.author | Daley, F | |
dc.contributor.author | Peckitt, C | |
dc.contributor.author | Tan, X | |
dc.contributor.author | Salman, A | |
dc.contributor.author | Lazaris, A | |
dc.contributor.author | Gazinska, P | |
dc.contributor.author | Berg, TJ | |
dc.contributor.author | Eltahir, Z | |
dc.contributor.author | Ritsma, L | |
dc.contributor.author | Van Rheenen, J | |
dc.contributor.author | Khashper, A | |
dc.contributor.author | Brown, G | |
dc.contributor.author | Nystrom, H | |
dc.contributor.author | Sund, M | |
dc.contributor.author | Van Laere, S | |
dc.contributor.author | Loyer, E | |
dc.contributor.author | Dirix, L | |
dc.contributor.author | Cunningham, D | |
dc.contributor.author | Metrakos, P | |
dc.contributor.author | Reynolds, AR | |
dc.date.accessioned | 2016-11-23T11:05:20Z | |
dc.date.issued | 2016-11-01 | |
dc.identifier.citation | Nature medicine, 2016, 22 (11), pp. 1294 - 1302 | |
dc.identifier.issn | 1078-8956 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/234 | |
dc.identifier.eissn | 1546-170X | |
dc.identifier.doi | 10.1038/nm.4197 | |
dc.description.abstract | The 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.format | Print-Electronic | |
dc.format.extent | 1294 - 1302 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.subject | HT29 Cells | |
dc.subject | Humans | |
dc.subject | Carcinoma | |
dc.subject | Carcinoma, Ductal, Breast | |
dc.subject | Carcinoma, Lobular | |
dc.subject | Breast Neoplasms | |
dc.subject | Colorectal Neoplasms | |
dc.subject | Liver Neoplasms | |
dc.subject | Neovascularization, Pathologic | |
dc.subject | Angiogenesis Inhibitors | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Cell Movement | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Actin-Related Protein 2-3 Complex | |
dc.subject | Gene Knockdown Techniques | |
dc.subject | Neoplasm Grading | |
dc.subject | Bevacizumab | |
dc.title | Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-09-09 | |
rioxxterms.versionofrecord | 10.1038/nm.4197 | |
rioxxterms.licenseref.startdate | 2016-11 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature medicine | |
pubs.issue | 11 | |
pubs.notes | 6 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-status | Published | |
pubs.volume | 22 | |
pubs.embargo.terms | 6 months | |
icr.researchteam | Medicine (RMH Smith Cunningham) | |
icr.researchteam | Tumour Biology | |
icr.researchteam | Translational Immunotherapy | |
dc.contributor.icrauthor | Bridgeman, Victoria | |
dc.contributor.icrauthor | Foo, Shane | |
dc.contributor.icrauthor | Nathan, Mark | |
dc.contributor.icrauthor | Daley, Frances | |
dc.contributor.icrauthor | Reynolds, Andrew | |