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https://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: international journal of cancer research and treatment, 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 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/627015 |
Published version: | http://ar.iiarjournals.org/content/34/12/7007.abstract |
Appears in Collections: | Aurora harvest 3 Medicine publications |
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