title: Exemestane blocks mesothelioma growth through downregulation of cAMP, pCREB and CD44 implicating new treatment option in patients affected by this disease.
abstract: BACKGROUND
  Recent evidence suggests that aromatase may be involved in the pathogenesis of malignant mesothelioma. Here, we evaluated the effect of exemestane, an inhibitor of aromatase, in the treatment of mesothelioma using in vitro and in vivo preclinical models.
  
  
  RESULTS
  We show a significant reduction of cell proliferation, survival, migration and block of cells in S phase of cell cycle in mesothelioma cells upon exemestane treatment. Moreover, we find that CD44, which is involved in mesothelioma cells migration, was modulated by exemestane via cAMP and pCREB. Most importantly, in mice mesothelioma xenograft exemestane causes a significant decrease in tumor size and the association pemetrexed/exemestane is more effective than pemetrexed/cisplatin.
  
  
  CONCLUSIONS
  The preclinical mesothelioma model suggests that exemestane might be beneficial in mesothelioma treatment.
authors.forename: Barbara
authors.initials: B
authors.lastname: Nuvoli
authors.forename: Sabrina
authors.initials: S
authors.lastname: Germoni
authors.forename: Carlotta
authors.initials: C
authors.lastname: Morosetti
authors.forename: Raffaela
authors.initials: R
authors.lastname: Santoro
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Cortese
authors.forename: Serena
authors.initials: S
authors.lastname: Masi
authors.forename: Iole
authors.initials: I
authors.lastname: Cordone
authors.affiliation: Molecular Medicine Area, Regina Elena National Cancer Institute, Rome 00144, Italy. galati@ifo.it.
authors.forename: Rossella
authors.initials: R
authors.lastname: Galati
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage*; D000818:Animals; D047072:Aromatase Inhibitors / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D000242:Cyclic AMP / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008654:Mesothelioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000086002:Mesothelioma, Malignant; D051379:Mice; D023041:Xenograft Model Antitumor Assays
chemical_list: D000730:Androstadienes; D047072:Aromatase Inhibitors; C497483:CD44 protein, human; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D018960:Hyaluronan Receptors; D000242:Cyclic AMP; C056516:exemestane; D002945:Cisplatin