Irene Zinonos1, Agatha Labrinidis1, Vasilios Liapis1, Shelley Hay1, Vasilios Panagopoulos1, Mark Denichilo1, Vladimir Ponomarev2, Wendy Ingman3, Gerald J Atkins4, David M Findlay4, Andrew C W Zannettino5, Andreas Evdokiou6. 1. Discipline of Surgery, Breast Cancer Research Unit, Basil Hetzel Institute and Centre for Personalised Cancer Medicine, University of Adelaide, Adelaide, SA, Australia. 2. Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, U.S.A. 3. Discipline of Surgery, Haematology - Oncology, Breast Biology Cancer Unit, Basil Hetzel Institute, University of Adelaide, Adelaide, SA, Australia. 4. Discipline of Orthopaedics and Trauma, University of Adelaide, Adelaide, SA, Australia. 5. Myeloma Research Laboratory, School of Medical Sciences, Faculty of Health Science and Centre for Personalised Cancer Medicine, University of Adelaide, Adelaide, SA, Australia. 6. Discipline of Surgery, Breast Cancer Research Unit, Basil Hetzel Institute and Centre for Personalised Cancer Medicine, University of Adelaide, Adelaide, SA, Australia andreas.evdokiou@adelaide.edu.au.
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. Copyright
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. Copyright
Authors: Rama Rathore; Jennifer E McCallum; Elizabeth Varghese; Ana-Maria Florea; Dietrich Büsselberg Journal: Apoptosis Date: 2017-07 Impact factor: 4.677
Authors: Vasilios Liapis; Irene Zinonos; Agatha Labrinidis; Shelley Hay; Vladimir Ponomarev; Vasilios Panagopoulos; Aneta Zysk; Mark DeNichilo; Wendy Ingman; Gerald J Atkins; David M Findlay; Andrew C W Zannettino; Andreas Evdokiou Journal: Cancer Med Date: 2016-01-09 Impact factor: 4.452