Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1073/pnas.0913912107

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

06/04/2010

Volume

107

Pages

6532 - 6537

Keywords

Antineoplastic Agents, Biomarkers, Biopsy, Cell Line, Tumor, Clinical Trials, Phase II as Topic, DNA Repair Enzymes, DNA-Binding Proteins, Histone Deacetylase Inhibitors, Humans, Lymphoma, T-Cell, Cutaneous, Proteasome Endopeptidase Complex, RNA, Small Interfering, Treatment Outcome