Journal article
Antitumor activities and on-target toxicities mediated by a TRAIL receptor agonist following cotreatment with panobinostat
BP Martin, AJ Frew, M Bots, S Fox, F Long, K Takeda, H Yagita, P Atadja, MJ Smyth, RW Johnstone
International Journal of Cancer | WILEY-BLACKWELL | Published : 2011
DOI: 10.1002/ijc.25594
Abstract
The recent development of novel targeted anticancer therapeutics such as histone deacetylase inhibitors (HDACi) and activators of the TRAIL pathway provide opportunities for the introduction of new treatment regimens in oncology. HDACi and recombinant TRAIL or agonistic anti-TRAIL receptor antibodies have been shown to induce synergistic tumor cell apoptosis and some therapeutic activity in vivo. Herein, we have used syngeneic preclinical models of human solid cancers to demonstrate that the HDACi panobinostat can sensitize tumor cells to apoptosis mediated by the anti-mouse TRAIL receptor antibody MD5-1. We demonstrate that the combination of panobinostat and MD5-1 can eradicate tumors grow..
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Awarded by Japan Society for the Promotion of Science
Funding Acknowledgements
[ "R.W.J. is the recipient of a collaborative research grant from Novartis for work involving panobinostat. P.A. is a paid employee of Novartis.", "R.W.J. is a Principal Research Fellow of the National Health and Medical Research Council of Australia (NHMRC) and supported by NHMRC Program and Project Grants, the Susan G. Komen Breast Cancer Foundation, the Prostate Cancer Foundation of Australia, Cancer Council Victoria, Victorian Breast Cancer Research Consortium and a research grant from Novartis. A.J.F. is supported by The Cancer Council Victoria. M.J.S. is a Senior Principal Research Fellow of the NHMRC and is supported by the Susan G. Komen Breast Cancer Foundation and NHMRC Program and Project Grants. M. B. is supported by a Rubicon research grant from Netherlands Organisation for Scientific Research (NWO). K.T. and H.Y. are supported by the Ministry of Education, Science and Culture, Japan." ]