Searching for targets for the systemic therapy of mesothelioma.
Malignant mesothelioma is an incurable disease associated with asbestos exposure arising in the pleural cavity and less frequently in the peritoneal cavity. Platinum-based combination chemotherapy with pemetrexed is the established standard of care. Multimodality approaches including surgery and radiotherapy are being investigated. Increasing knowledge about the molecular characteristics of mesothelioma had led to the identification of novel potential targets for systemic therapy. Current evidence suggests pathways activated in response to merlin deficiency, including Pi3K/mTOR and the focal adhesion kinase, as well as immunotherapeutic approaches to be most promising. This review elaborates on the rationale behind targeted approaches that have been and are undergoing exploration in mesothelioma and summarizes available clinical results and ongoing efforts to improve the systemic therapy of mesothelioma.
Department of Oncology, University Hospital, Zürich rolf.stahel@usz.ch.
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Stahel
Department of Thoracic Surgery, University Hospital, Zürich.
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Weder
Department of Oncology, University Hospital, Zürich.
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Felley-Bosco
Department of Oncology, University Hospital, Zürich.
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Petrausch
Department of Oncology, University Hospital, Zürich.
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Curioni-Fontecedro
Department of Thoracic Surgery, University Hospital, Zürich.
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Schmitt-Opitz
Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
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Peters
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D000068338:Everolimus / Q000008:administration & dosage; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008654:Mesothelioma / Q000188:drug therapy* / Q000378:metabolism; D000086002:Mesothelioma, Malignant; D058990:Molecular Targeted Therapy / Q000379:methods*; D000068437:Pemetrexed / Q000008:administration & dosage; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D002945:Cisplatin; D000068338:Everolimus; D051416:Focal Adhesion Protein-Tyrosine Kinases; D000068437:Pemetrexed; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases
immunotherapy; mesothelioma; targeted therapy