Imperial College London
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ProfessorPhilipMolyneaux

Faculty of Medicine, National Heart & Lung Institute

Professor of Interstitial Lung Disease
 
 
 
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Contact

 

p.molyneaux

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Conforti:2017:10.18632/oncotarget.17114,
author = {Conforti, F and Davies, ER and Calderwood, CJ and Thatcher, TH and Jones, MG and Smart, DE and Mahajan, S and Alzetani, A and Havelock, T and Maher, TM and Molyneaux, PL and Thorley, AJ and Tetley, TD and Warner, JA and Packham, G and Ganesan, A and Skipp, PJ and Marshall, BJ and Richeldi, L and Sime, PJ and O'Reilly, KMA and Davies, DE},
doi = {10.18632/oncotarget.17114},
journal = {Oncotarget},
pages = {48737--48754},
title = {The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis.},
url = {http://dx.doi.org/10.18632/oncotarget.17114},
volume = {8},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects.
AU  - Conforti,F
AU  - Davies,ER
AU  - Calderwood,CJ
AU  - Thatcher,TH
AU  - Jones,MG
AU  - Smart,DE
AU  - Mahajan,S
AU  - Alzetani,A
AU  - Havelock,T
AU  - Maher,TM
AU  - Molyneaux,PL
AU  - Thorley,AJ
AU  - Tetley,TD
AU  - Warner,JA
AU  - Packham,G
AU  - Ganesan,A
AU  - Skipp,PJ
AU  - Marshall,BJ
AU  - Richeldi,L
AU  - Sime,PJ
AU  - O'Reilly,KMA
AU  - Davies,DE
DO  - 10.18632/oncotarget.17114
EP  - 48754
PY  - 2017///
SN  - 1949-2553
SP  - 48737
TI  - The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis.
T2  - Oncotarget
UR  - http://dx.doi.org/10.18632/oncotarget.17114
UR  - http://hdl.handle.net/10044/1/48359
VL  - 8
ER  -
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