Zinonos, I.Labrinidis, A.Liapis, V.Hay, S.Panagopoulos, V.Denichilo, M.Ponomarev, V.Ingman, W.Atkins, G.Findlay, D.Zannettino, A.Evdokiou, A.2016-06-152016-06-152014Anticancer Research, 2014; 34(12):7007-70200250-70051791-7530http://hdl.handle.net/2440/99694Background/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.enCopyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reservedApoptosis; Apo2L/TRAIL; drozitumab; drug resistance; chemotherapy; breast cancerJournal article00300171250003466897000162-s2.0-84918501194163361Liapis, V. [0000-0002-2354-3521]Panagopoulos, V. [0000-0002-6879-1262]Ingman, W. [0000-0003-3116-2902]Atkins, G. [0000-0002-3123-9861]Zannettino, A. [0000-0002-6646-6167]Evdokiou, A. [0000-0001-8321-9806]