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|Title:||Doxorubicin overcomes resistance to drozitumab by antagonizing inhibitor of apoptosis proteins (IAPS)|
|Citation:||Anticancer Research, 2014; 34(12):7007-7020|
|Publisher:||International Institute of Anticancer Research|
|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|
|Appears in Collections:||Medicine publications|
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