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Cited by 454

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases

Open access
Frentzas, Sophia, Simoneau, Eve, Bridgeman, Victoria L, Vermeulen, Peter B, Foo, Shane, Kostaras, Eleftherios, Nathan, Mark R, Wotherspoon, Andrew, Gao, Zu-hua, Shi, Yu, Van den Eynden, Gert, Daley, Frances, Peckitt, Clare, Tan, Xianming, Salman, Ayat, Lazaris, Anthoula, Gazinska, Patrycja, Berg, Tracy J, Eltahir, Zak, Ritsma, Laila, van Rheenen, Jacco, Khashper, Alla, Brown, Gina, Nyström, Hanna, Sund, Malin, Van Laere, Steven, Loyer, Evelyne, Dirix, Luc, Cunningham, David, Metrakos, Peter, Reynolds, Andrew R·2016·Nature Medicine
DOI 10.1038/nm.4197
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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.

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Metadata

Authors
Frentzas, S., Simoneau, E., Bridgeman, V. L., Vermeulen, P. B., Foo, S., Kostaras, E., Nathan, M. R., Wotherspoon, A., Gao, Z.-H., Shi, Y., Van den Eynden, G., Daley, F., Peckitt, C., Tan, X., Salman, A., Lazaris, A., Gazinska, P., Berg, T. J., Eltahir, Z., Ritsma, L., van Rheenen, J., Khashper, A., Brown, G., Nyström, H., Sund, M., Van Laere, S., Loyer, E., Dirix, L., Cunningham, D., Metrakos, P., & Reynolds, A. R.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2016-10-17
Volume
22
Issue
11
Pages
1294-1302
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.4197
OpenAlex
W2533236332
Cited by
454
References
7
FWCI
18.96
Type
journal article
Language
en
Open access
green

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