title: Valproic acid improves second-line regimen of small cell lung carcinoma in preclinical models.
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.
authors.affiliation: Molecular Biology (GxABT), University of Liege (ULg), Gembloux, Belgium; Molecular and Cellular Epigenetics (GIGA), ULg, Liege, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA), ULg, Liege, Belgium; Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Hubaux
authors.affiliation: Molecular Biology (GxABT), University of Liege (ULg), Gembloux, Belgium; Molecular and Cellular Epigenetics (GIGA), ULg, Liege, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA), ULg, Liege, Belgium; Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA.
authors.forename: Fabian
authors.initials: F
authors.lastname: Vandermeers
authors.affiliation: Molecular Biology (GxABT), University of Liege (ULg), Gembloux, Belgium; Molecular and Cellular Epigenetics (GIGA), ULg, Liege, Belgium.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Cosse
authors.affiliation: Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Crisanti
authors.affiliation: Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Kapoor
authors.affiliation: Pulmonary, Allergy and Critical Care Division, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albelda
authors.affiliation: Department of Multidisciplinary Oncology and Therapeutic Innovations, Aix Marseille University, Marseille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Mascaux
authors.affiliation: Experimental Pathology, GIGA-Cancer, ULg, Liège, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.affiliation: Experimental Pathology, GIGA-Cancer, ULg, Liège, Belgium.
authors.forename: Pascale
authors.initials: P
authors.lastname: Hubert
authors.affiliation: Molecular Biology (GxABT), University of Liege (ULg), Gembloux, Belgium; Molecular and Cellular Epigenetics (GIGA), ULg, Liege, Belgium; Interdisciplinary Cluster for Applied Genoproteomics (GIGA), ULg, Liege, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Willems