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dc.contributor.authorBen-Batalla, Isabel
dc.contributor.authorCubas-Cordova, Miguel
dc.contributor.authorUdonta, Florian
dc.contributor.authorWroblewski, Mark
dc.contributor.authorWaizenegger, Jonas S.
dc.contributor.authorJanning, Melanie
dc.contributor.authorSawall, Stefanie
dc.contributor.authorGensch, Victoria
dc.contributor.authorZhao, Lin
dc.contributor.authorMartinez, Inigo Zubiavrre
dc.contributor.authorRiecken, Kristoffer
dc.contributor.authorFehse, Boris
dc.contributor.authorPantel, Klaus
dc.contributor.authorBokemeyer, Carsten
dc.contributor.authorLoges, Sonja
dc.date.accessioned2022-04-20T09:09:06Z
dc.date.available2022-04-20T09:09:06Z
dc.date.issued2015-01-31
dc.description.abstractAnti-angiogenic therapies were approved for different cancers. However, significant primary and secondary resistance hampers efficacy in several tumor types including breast cancer. Thus, we need to develop clinically applicable strategies to enhance efficacy of anti-angiogenic drugs. We report that anti-angiogenic therapies can induce upregulation of cyclooxygenase-2 (Cox-2) and of its product prostaglandin E2 (PGE2) in breast cancer models. Upon Cox-2 inhibition PGE<sub>2</sub> levels were normalized and efficacy of antivascular endothelial growth factor receptor 2 (anti-VEGFR-2) antibodies and sunitinib was enhanced. Interestingly, both treatments exerted additive anti-angiogenic effects. Following Cox-2 inhibition, we observed reduced infiltration of tumors with cancer-associated fibroblasts (CAFs) and lower levels of pro-angiogenic factors active besides the VEGF axis including hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF2). Mechanistic studies indicated that Cox-2 inhibition reduced PGE<sub>2</sub>-induced migration and proliferation of CAFs via inhibiting phosphorylation of Akt. Hence, Cox-2 inhibition can increase efficacy of anti-angiogenic treatments and our findings might pave the road for clinical investigations of concomitant blockade of Cox-2 and VEGF-signaling.en_US
dc.identifier.citationBen-Batalla I, Cubas-Cordova M, Udonta, Wroblewski M, Waizenegger JS, Janning M, Sawall S, Gensch, Zhao, Martinez IZ, Riecken K, Fehse B, Pantel K, Bokemeyer C, Loges S. Cyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugs. OncoTarget. 2015;6(8):6341-6358en_US
dc.identifier.cristinIDFRIDAID 1257102
dc.identifier.doi10.18632/oncotarget.3437
dc.identifier.issn1949-2553
dc.identifier.urihttps://hdl.handle.net/10037/24816
dc.language.isoengen_US
dc.publisherImpact Journalsen_US
dc.relation.journalOncoTarget
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2015 The Author(s)en_US
dc.titleCyclooxygenase-2 blockade can improve efficacy of VEGF-targeting drugsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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