Abstract
With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to first-line therapy, relapses are frequent and further treatments are disappointing. The goal of the study was to improve second-line therapy of SCLC.
The effect of chemotherapeutic agents was evaluated in cell lines (apoptosis, reactive oxygen species, and RNA and protein expression) and in mouse models (tumour development).
We demonstrate here that valproic acid, a histone deacetylase inhibitor, improves the efficacy of a second-line regimen (vindesine, doxorubicin and cyclophosphamide) in SCLC cells and in mouse models.
Transcriptomic profiling integrating microRNA and mRNA data identifies key signalling pathways in the response of SCLC cells to valproic acid, opening new prospects for improved therapies.
Abstract
Valproic acid improves second-line regimen of SCLC response in preclinical models http://ow.ly/Rsyd8
Footnotes
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Support statement: The work was supported by the Fonds National de la Recherche Scientifique (FNRS), the Télévie, the Interuniversity Attraction Poles programme BELVIR initiated by the Belgian Science Policy Office, the Action de Recherche Concertée Glyvir of the Communauté française de Belgique, the Belgian Foundation against Cancer, the Sixth Research Framework Programme of the European Union (project INCA LSHC-CT-2005-018704), the Neoangio excellence programme and the Partenariat Public Privé INCA of the Direction générale des Technologies, de la Recherche et de l'Energie/DG06 of the Walloon government, the Centre anticancéreux près ULg, the Synbiofor and Agricultureislife projects of GxABT, the ULg Fonds Spéciaux pour la Recherche, the Plan Cancer of the Service Public Fédéral. L. Willems (research director) is member of the FNRS. Funding information for this article has been deposited with FundRef.
Conflict of interest: Disclosures can be found alongside this article at openres.ersjournals.com
- Received June 2, 2015.
- Accepted August 24, 2015.
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