title: Anti-angiogenic therapies for malignant pleural mesothelioma.
abstract: BACKGROUND
  Malignant pleural mesothelioma (MPM) is a disease with a dismal prognosis. Currently available treatments have modest results. Therefore, new agents and new treatment strategies are eagerly awaited by patients and clinicians. Preclinical and clinical studies have shown that angiogenesis plays a very important role in MPM. Therefore, a great hope has been placed in the use of anti-angiogenic agents in this disease.
  
  
  METHODS
  Studies regarding anti-angiogenic treatments in MPM with bevacizumab, tyrosine-kinase inhibitors (TKIs) and other agents were critically analyzed, with an overview of ongoing trials and future perspectives, including research on biomarkers.
  
  
  CONCLUSIONS
  The clinical use of angiogenesis inhibitors in MPM patients has resulted more challenging than anticipated. The intrinsic complexity of neo-angiogenesis, and its redundant regulatory mechanisms, suggests that multiple and different biomarkers are needed to predict efficacy of anti-angiogenic agents and to monitor their biological and therapeutic effects. The growing understanding of the molecular alterations and key pathways that underlie the resistance to VEGF inhibitors will allow to design studies of the combination of agents targeting these pathways with anti-VEGF therapies. Only a tight integration of preclinical and clinical studies will allow to achieve a real progress in MPM patients with this therapeutic strategy.
authors.affiliation: Thoracic and GU Oncology Unit, Cliniche Humanitas Gavazzeni, Via M. Gavazzeni 21, 24125 Bergamo, Italy. giovanni_luca.ceresoli@gavazzeni.it
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Ceresoli
authors.forename: Paolo Andrea
authors.initials: PA
authors.lastname: Zucali
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000379:methods; D016503:Drug Delivery Systems; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008654:Mesothelioma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010997:Pleural Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015415:Biomarkers; D042461:Vascular Endothelial Growth Factor A