HR23B is a biomarker for tumor sensitivity to HDAC inhibitor-based therapy
- 22 March 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 107 (14), 6532-6537
- https://doi.org/10.1073/pnas.0913912107
Abstract
Histone deacetylase (HDAC) inhibitors are emergent cancer drugs. HR23B is a candidate cancer biomarker identified in a genome-wide loss-of-function screen which influences sensitivity to HDAC inhibitors. Because HDAC inhibitors have found clinical utility in cutaneous T-cell lymphoma (CTCL), we evaluated the role of HR23B in CTCL cells. Our results show that HR23B governs the sensitivity of CTCL cells to HDAC inhibitors. Furthermore, proteasome activity is deregulated in HDAC inhibitor-treated CTCL cells through a mechanism dependent upon HR23B, and HDAC inhibitors sensitize CTCL cells to the effects of proteasome inhibitors. The predictive power of HR23B for clinical response to HDAC inhibitors was investigated through an analysis of a unique collection of CTCL biopsies taken from a phase II clinical trial, where there was a frequent coincidence between HR23B expression and clinical response to HDAC inhibitor. Our study supports the personalized medicine approach for treating cancer and the increasing drive to translate laboratory-based findings into clinical utility.Keywords
This publication has 22 references indexed in Scilit:
- HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagyThe EMBO Journal, 2010
- Phase I Study of Vorinostat in Combination with Bortezomib for Relapsed and Refractory Multiple MyelomaClinical Cancer Research, 2009
- HDAC inhibitor-based therapies and haematological malignancyAnnals Of Oncology, 2009
- Caspase-8 dependent histone acetylation by a novel proteasome inhibitor, NPI-0052: a mechanism for synergy in leukemia cellsBlood, 2009
- Drug Insight: histone deacetylase inhibitor-based therapies for cutaneous T-cell lymphomasNature Clinical Practice Oncology, 2008
- Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drugNature Biotechnology, 2007
- Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL)Blood, 2006
- Keynote review: Chromatin control and cancer-drug discovery: realizing the promiseDrug Discovery Today, 2006
- Selective Induction of Apoptosis by Histone Deacetylase Inhibitor SAHA in Cutaneous T-Cell Lymphoma Cells: Relevance to Mechanism of Therapeutic ActionJournal of Investigative Dermatology, 2005
- Basic principles of ROC analysisSeminars in Nuclear Medicine, 1978