Journal article
HDAC inhibitors induce tumor-cell-selective pro-apoptotic transcriptional responses
JE Bolden, W Shi, K Jankowski, CY Kan, L Cluse, BP Martin, KL MacKenzie, GK Smyth, RW Johnstone
Cell Death and Disease | SPRINGERNATURE | Published : 2013
DOI: 10.1038/cddis.2013.9
Open access
Abstract
The identification of recurrent somatic mutations in genes encoding epigenetic enzymes has provided a strong rationale for the development of compounds that target the epigenome for the treatment of cancer. This notion is supported by biochemical studies demonstrating aberrant recruitment of epigenetic enzymes such as histone deacetylases (HDACs) and histone methyltransferases to promoter regions through association with oncogenic fusion proteins such as PML-RARα and AML1-ETO. HDAC inhibitors (HDACi) are potent inducers of tumor cell apoptosis; however, it remains unclear why tumor cells are more sensitive to HDACi-induced cell death than normal cells. Herein, we assessed the biological and ..
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Awarded by Novartis
Funding Acknowledgements
Dr. Johnstone's work has been funded by a research grant from Novartis.We thank Ben Martin, Christopher Clarke and Richard Pearson for constructive criticism and helpful advice, and William Hahn for normal and transformed cell lines. RWJ 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, Cancer Council Victoria, The Victorian Cancer Agency, The Leukemia Foundation of Australia and the Victorian Breast Cancer Research Consortium. JEB was supported by The Cancer Research Institute Predoctoral Emphasis Pathway in Tumor Immunology. KLM was supported by funds from NHMRC, Cancer Institute NSW and NSW Cancer Council. GKS is a Senior Research Fellowship of the NHMRC. GKS and WS are supported by NHMRC Program Grant 490037.