title: Preliminary data suggestive of a novel translational approach to mesothelioma treatment: imatinib mesylate with gemcitabine or pemetrexed.
abstract: 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 beta (PDGFRbeta). PDGFRbeta 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 PDGFRbeta 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.
authors.affiliation: DISCAFF Department and DFBC Center, University of Piemonte Orientale A Avogadro, 28100 Novara, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Bertino
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Dario
authors.initials: D
authors.lastname: Barbone
authors.forename: Serena
authors.initials: S
authors.lastname: Germano
authors.forename: Sara
authors.initials: S
authors.lastname: Busacca
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pinato
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Tassi
authors.forename: Roberto
authors.initials: R
authors.lastname: Favoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gaudino
authors.forename: Luciano
authors.initials: L
authors.lastname: Mutti
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D016923:Cell Death; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D016236:Genes, fms; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000068877:Imatinib Mesylate; D008654:Mesothelioma / Q000188:drug therapy* / Q000378:metabolism; D000068437:Pemetrexed; D010879:Piperazines / Q000008:administration & dosage; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D001549:Benzamides; D005971:Glutamates; D010879:Piperazines; D011743:Pyrimidines; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D000093542:Gemcitabine