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HDAC11 is a novel drug target in carcinomas

Item Type:Article
Title:HDAC11 is a novel drug target in carcinomas
Creators Name:Deubzer, H.E. and Schier, M.C. and Oehme, I. and Lodrini, M. and Haendler, B. and Sommer, A. and Witt, O.
Abstract:Inhibition of histone deacetylase (HDAC) activity as stand-alone or combination therapy represents a promising therapeutic approach in oncology. The pan- or class I HDAC inhibitors (HDACi) currently approved or in clinical studies for oncology give rise to dose-limiting toxicities, presumably because of the inhibition of several HDACs. This could potentially be overcome by selective blockade of single HDAC family members. Here we report that HDAC11, the most recently identified zinc-dependent HDAC, is overexpressed in several carcinomas as compared to corresponding healthy tissues. HDAC11 depletion is sufficient to cause cell death and to inhibit metabolic activity in HCT-116 colon, PC-3 prostate, MCF-7 breast and SK-OV-3 ovarian cancer cell lines. The antitumoral effect induced can be mimicked by enforced expression of a catalytically impaired HDAC11 variant, suggesting that inhibition of the enzymatic activity of HDAC11 by small molecules could trigger the desired phenotypic changes. HDAC11 depletion in normal cells causes no changes in metabolic activity and viability, strongly suggesting that tumor-selective effects can be achieved. Altogether, our data show that HDAC11 plays a critical role in cancer cell survival and may represent a novel drug target in oncology.
Keywords:Chromatin Modulation, Targeted Therapy, Histone Deacetylase, Colon Cancer, Prostate Cancer
Source:International Journal of Cancer
ISSN:0020-7136
Publisher:Wiley (U.S.A.)
Volume:132
Number:9
Page Range:2200-2208
Date:1 May 2013
Official Publication:https://doi.org/10.1002/ijc.27876
PubMed:View item in PubMed

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