Doxorubicin overcomes resistance to drozitumab by antagonizing inhibitor of apoptosis proteins (IAPS)

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dc.contributor.authorZinonos, I.
dc.contributor.authorLabrinidis, A.
dc.contributor.authorLiapis, V.
dc.contributor.authorHay, S.
dc.contributor.authorPanagopoulos, V.
dc.contributor.authorDenichilo, M.
dc.contributor.authorPonomarev, V.
dc.contributor.authorIngman, W.
dc.contributor.authorAtkins, G.
dc.contributor.authorFindlay, D.
dc.contributor.authorZannettino, A.
dc.contributor.authorEvdokiou, A.
dc.date.issued2014
dc.description.abstractBackground/Aim: Drozitumab is a fully human agonistic monoclonal antibody that binds to death receptor DR5 and induces apoptosis. However, drozitumab resistance is a major obstacle limiting anticancer efficacy. Materials and Methods: We examined the potential for the chemotherapeutic agent doxorubicin to overcome resistance against drozitumab-resistant breast cancer cells both in vitro and in vivo. Results: Treatment with doxorubicin increased cell surface expression of DR5, reduced levels of Inhibitors of Apoptosis Proteins (cIAPs) and re-sensitised cells to drozitumab-induced apoptosis. Animals implanted with resistant breast cancer cells into the mammary fat pad and treated with a combination of drozitumab and doxorubicin showed inhibition of tumor growth and a substantial delay in tumor progression compared to untreated controls and mice treated with each agent alone. Conclusion: These results suggest that combination of drozitumab with chemotherapy and agents that modulate IAP levels could potentially be a useful strategy in the treatment of breast cancer.
dc.description.statementofresponsibilityIrene Zinonos, Agatha Labrinidis, Vasilios Liapis, Shelley Hay, Vasilios Panagopoulos, Mark Denichilo, Vladimer Ponomarev, Wendy Ingman, Gerald J. Atkins, David M. Findlay, Andrew C. W. Zannettino and Andreas Evdokiou
dc.identifier.citationAnticancer Research, 2014; 34(12):7007-7020
dc.identifier.issn0250-7005
dc.identifier.issn1791-7530
dc.identifier.orcidLiapis, V. [0000-0002-2354-3521]
dc.identifier.orcidPanagopoulos, V. [0000-0002-6879-1262]
dc.identifier.orcidIngman, W. [0000-0003-3116-2902]
dc.identifier.orcidAtkins, G. [0000-0002-3123-9861]
dc.identifier.orcidZannettino, A. [0000-0002-6646-6167]
dc.identifier.orcidEvdokiou, A. [0000-0001-8321-9806]
dc.identifier.urihttp://hdl.handle.net/2440/99694
dc.language.isoen
dc.publisherInternational Institute of Anticancer Research
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/627015
dc.rightsCopyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
dc.source.urihttp://ar.iiarjournals.org/content/34/12/7007.abstract
dc.subjectApoptosis; Apo2L/TRAIL; drozitumab; drug resistance; chemotherapy; breast cancer
dc.titleDoxorubicin overcomes resistance to drozitumab by antagonizing inhibitor of apoptosis proteins (IAPS)
dc.typeJournal article
pubs.publication-statusPublished

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