title: Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies.
abstract: Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally linked to occupational exposure to asbestos. Familial clusters of mesotheliomas have been observed in settings of genetic predisposition. Mesothelioma incidence is anticipated to increase worldwide in the next two decades. Novel treatments are needed, as current treatment modalities may improve the quality of life, but have shown modest effects in improving overall survival. Increasing knowledge on the molecular characteristics of mesothelioma has led to the development of novel potential therapeutic strategies, including: molecular targeted approaches, that is the inhibition of vascular endothelial growth factor with bevacizumab; immunotherapy with chimeric monoclonal antibody, immunotoxin, antibody drug conjugate, vaccine and viruses; inhibition of asbestos-induced inflammation, that is aspirin inhibition of HMGB1 activity may decrease or delay mesothelioma onset and/or growth. We elaborate on the rationale behind new therapeutic strategies, and summarize available preclinical and clinical results, as well as efforts still ongoing.
authors: a 1 University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, Hawai'i, USA.
authors: Angela
authors: A
authors: Bononi
authors: a 1 University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, Hawai'i, USA.|b 2 Molecular Biosciences and Bioengineering, University of Hawai'i at Mānoa, Honolulu, Hawai'i, USA.
authors: Andrea
authors: A
authors: Napolitano
authors: c 3 Department of Cardiothoracic Surgery, Division of Thoracic Surgery, Langone Medical Center, New York University, New York, USA.
authors: Harvey I
authors: HI
authors: Pass
authors: a 1 University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, Hawai'i, USA.
authors: Haining
authors: H
authors: Yang
authors: a 1 University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, Hawai'i, USA.
authors: Michele
authors: M
authors: Carbone
mesh_terms: D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D008654:Mesothelioma / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D000086002:Mesothelioma, Malignant; D058990:Molecular Targeted Therapy / Q000379:methods; D010534:Peritoneal Neoplasms / Q000209:etiology / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D010997:Pleural Neoplasms / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*
keywords: BAP1; HMGB1; asbestos; aspirin; carcinogenesis; immunotherapy; mesothelioma; molecular therapy; polyclonal tumors