Doxorubicin overcomes resistance to drozitumab by antagonizing inhibitor of apoptosis proteins (IAPs) Journal Article


Authors: Zinonos, I.; Labrinidis, A.; Liapis, V.; Hay, S.; Panagopoulos, V.; Denichilo, M.; Ponomarev, V.; Ingman, W.; Atkins, G. J.; Findlay, D. M.; Zannettino, A. C. W.; Evdokiou, A.
Article Title: Doxorubicin overcomes resistance to drozitumab by antagonizing inhibitor of apoptosis proteins (IAPs)
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 drozitumabresistant 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: chemotherapy; apoptosis; drug resistance; apo2l/trail; breast cancer.; drozitumab
Journal Title: Anticancer Research
Volume: 34
Issue: 12
ISSN: 0250-7005
Publisher: International Institute of Anticancer Research  
Date Published: 2014-12-01
Start Page: 7007
End Page: 7020
Language: English
PROVIDER: scopus
PUBMED: 25503127
DOI/URL:
Notes: Export Date: 2 January 2015 -- Source: Scopus