Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma

GM Matthews; M Lefebure; MA Doyle; J Shortt; J Ellul; M Chesi; K-M Banks; E Vidacs; D Faulkner; P Atadja; PL Bergsagel; RW Johnstone

Journal article

Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma

GM Matthews, M Lefebure, MA Doyle, J Shortt, J Ellul, M Chesi, K-M Banks, E Vidacs, D Faulkner, P Atadja, PL Bergsagel, RW Johnstone

CELL DEATH & DISEASE | NATURE PUBLISHING GROUP | Published : 2013

DOI: 10.1038/cddis.2013.306

Download PDF

Abstract

Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinostat, romidepsin) and novel combination therapies using in vitro human MM cell lines and in vivo preclinical screening utilizing syngeneic transplanted Vk*MYC MM. HDACi were combined with ABT-737, which targets the intrinsic apoptosis pathway, recombinant human tumour necrosis factor-related apoptosis-inducing ligand (rhTRAIL/MD5-1), that activates the extrinsic apoptosis pathway o..

View full abstract

University of Melbourne Researchers

Jake Shortt Author The Sir Peter Maccallum Department of Oncology

Jason Ellul Author The Sir Peter Maccallum Department of Oncology

Ricky Johnstone Author The Sir Peter Maccallum Department of Oncology

Maria Doyle Author The Sir Peter Maccallum Department of Oncology

Grants

Awarded by National Institutes of Health

Awarded by National Cancer Institute

Awarded by NATIONAL CANCER INSTITUTE

Awarded by NATIONAL INSTITUTE ON AGING

Funding Acknowledgements

We thank Dr Hideo Yagita for the provision of MD5-1. GMM was supported by funding from the National Health and Medical Research Council (NHMRC) of Australia. JS was supported by funding from the Leukaemia Foundation of Australia and the Co-operative Research Centre for Biomedical Imaging Development. RWJ is a Principal Research Fellow of the NHMRC of Australia and supported by NHMRC Program and Project Grants, the Susan G Komen Breast Cancer Foundation, Cancer Council Victoria, The Leukaemia Foundation of Australia, Victorian Breast Cancer Research Consortium and the Victorian Cancer Agency. ML is supported by the Leukaemia Foundation of Australia. This work was supported by National Institutes of Health Grant AG20686, National Cancer Institute Grant CA136671 (PLB) and by the Multiple Myeloma Research Foundation (MC).