RT Journal Article SR Electronic T1 Preliminary data suggestive of a novel translational approach to mesothelioma treatment: imatinib mesylate with gemcitabine or pemetrexed JF Thorax JO Thorax FD BMJ Publishing Group Ltd and British Thoracic Society SP 690 OP 695 DO 10.1136/thx.2006.069872 VO 62 IS 8 A1 Bertino, Pietro A1 Porta, Camillo A1 Barbone, Dario A1 Germano, Serena A1 Busacca, Sara A1 Pinato, Sabrina A1 Tassi, Giancarlo A1 Favoni, Roberto A1 Gaudino, Giovanni A1 Mutti, Luciano YR 2007 UL http://thorax.bmj.com/content/62/8/690.abstract AB Background: Malignant mesothelioma is a cancer which is refractory to current treatments. Imatinib mesylate is a selective inhibitor of tyrosine kinases such as bcr-abl, c-Kit, c-Fms and platelet derived growth factor receptor β (PDGFRβ). PDGFRβ is often overexpressed in mesothelioma cells and is a therapeutic target for imatinib in some solid tumours. A study was undertaken to assess whether imatinib alone or combined with chemotherapeutic agents may be effective for treating mesothelioma. Methods: Cultures from mesothelioma MMP, REN and ISTMES2 cell lines were treated with imatinib alone or in combination with a chemotherapeutic agent. Results: Imatinib induced cytotoxicity and apoptosis selectively on PDGFRβ positive mesothelioma cells via blockade of receptor phosphorylation and interference with the Akt pathway. Of the chemotherapeutic agents tested in combination with imatinib, a synergistic effect was obtained with gemcitabine and pemetrexed. Conclusions: This study provides a rationale for a novel translational approach to the treatment of mesothelioma which relies on enhancement of tumour chemosensitivity by inhibition of Akt.