Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/99694
Type: Journal article
Title: Doxorubicin overcomes resistance to drozitumab by antagonizing inhibitor of apoptosis proteins (IAPS)
Author: Zinonos, I.
Labrinidis, A.
Liapis, V.
Hay, S.
Panagopoulos, V.
Denichilo, M.
Ponomarev, V.
Ingman, W.
Atkins, G.
Findlay, D.
Zannettino, A.
Evdokiou, A.
Citation: Anticancer Research, 2014; 34(12):7007-7020
Publisher: International Institute of Anticancer Research
Issue Date: 2014
ISSN: 0250-7005
1791-7530
Statement of
Responsibility: 
Irene 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
Abstract: Background/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.
Keywords: Apoptosis; Apo2L/TRAIL; drozitumab; drug resistance; chemotherapy; breast cancer
Rights: Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
RMID: 0030017125
Grant ID: http://purl.org/au-research/grants/nhmrc/627015
Published version: http://ar.iiarjournals.org/content/34/12/7007.abstract
Appears in Collections:Medicine publications

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