期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 14, 页码 6532-6537出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0913912107
关键词
cancer; histone deacetylase inhibitor; biomarker; proteasome; clinical trial
资金
- Cancer Research UK
- Medical Research Council
- Leukemia Research Council
- Association for International Cancer Research
- European Union
- NIHR Biomedical Research Centre, Oxford, United Kingdom
- MRC [G9400953, G0500905] Funding Source: UKRI
- Medical Research Council [G9400953, G0500905] Funding Source: researchfish
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.
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