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ORIGINAL ARTICLE Histone Deacetylase Inhibitor Romidepsin Enhances Anti-Tumor Effect of Erlotinib in Non-small Cell Lung Cancer (NSCLC) Cell Lines Wei Zhang, PhD,* Michael Peyton, PhD,* Yang Xie, PhD,†‡ Junichi Soh, MD,* John D. Minna, MD,*†§ Adi F. Gazdar, MD,*†¶ and Eugene P. Frenkel, MD†§ he epidermal growth factor receptor (EGFR) belongs to Introduction: Most epidermal growth factor receptor (EGFR) mu- Tthe EGFR family of tyrosine kinase receptors. Upon tant non-small cell lung cancers (NSCLCs) are sensitive to EGFR activation, EGFR can promote cell proliferation and survival tyrosine kinase inhibitors (TKIs) such as erlotinib or geﬁtinib, but through Ras/MEK/MAPK and/or PI3K/AKT signaling path- many EGFR wild type NSCLCs are resistant to TKIs. In this study, ways. In recent years, non-small cell lung cancers (NSCLCs) we examined the effects of the histone deacetylase inhibitor, ro- containing EGFR mutations have been found to be sensitive midepsin, in combination with erlotinib, in NSCLC cell lines and to EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib xenografts. (Tarceva) or geﬁtinib (Iressa), and these drugs have been Methods: For in vitro studies, nine NSCLC cell lines with varying 3,4 successfully used in the therapy for such patients. Unfor- mutation status and histology were treated with
Journal of Thoracic Oncology – Wolters Kluwer Health
Published: Feb 1, 2009
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