The HDAC inhibitor panobinostat (LBH589) inhibits mesothelioma and lung cancer cells in vitro and in vivo with particular efficacy for small cell lung cancer

• Published in: Molecular cancer therapeutics 2009-08, Vol.8 (8), p.2221-2231
• Main Authors: Crisanti, M Cecilia, Wallace, Africa F, Kapoor, Veena, Vandermeers, Fabian, Dowling, Melissa L, Pereira, Luana P, Coleman, Kara, Campling, Barbara G, Fridlender, Zvi G, Kao, Gary D, Albelda, Steven M
• Format: Article
• Language: English
• Subjects: Carcinoma, Small Cell - drug therapy; Carcinoma, Small Cell - enzymology; Carcinoma, Small Cell - pathology; Cell Line, Tumor; etoposide and panobinostat; Etoposide plus HDACi; HDACi; Histone Deacetylase Inhibitors - pharmacology; Human health sciences; Humans; Hydroxamic Acids - pharmacology; Indoles; Lung Cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - enzymology; Lung Neoplasms - pathology; Mesothelioma; Mesothelioma - drug therapy; Mesothelioma - pathology; Oncologie; Oncology; Sciences de la santé humaine; Small Cell Lung Cancer
• ISSN: 1535-7163; 1538-8514; 1538-8514
• DOI: 10.1158/1535-7163.MCT-09-0138

Lung cancer is the leading cause of cancer deaths in the United States. Current therapies are inadequate. Histone deacetylase inhibitors (HDACi) are a recently developed class of anticancer agents that cause increased acetylation of core histones and nonhistone proteins leading to modulation of gene expression and protein activity involved in cancer cell growth and survival pathways. We examined the efficacy of the HDACi panobinostat (LBH589) in a wide range of lung cancers and mesotheliomas. Panobinostat was cytotoxic in almost all 37 cancer cell lines tested. IC 50 and LD 50 values were in the low nmol/L range (4–470 nmol/L; median, 20 nmol/L). Small cell lung cancer (SCLC) cell lines were among the most sensitive lines, with LD 50 values consistently