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Molecular pathogenesis of malignant mesothelioma

Published online by Cambridge University Press:  24 May 2012

Philip A. Rascoe ,
Daniel Jupiter ,
Xiaobo Cao ,
James E. Littlejohn  and
W. Roy Smythe
Philip A. Rascoe*
Affiliation:
Texas A&M Health Science Center College of Medicine, Temple, TX, USA Department of Surgery, Scott and White Memorial Hospital and Clinic, Temple, TX, USA Department of Surgery, Olin E. Teague Veterans' Medical Center, Temple, TX, USA
Daniel Jupiter
Affiliation:
Texas A&M Health Science Center College of Medicine, Temple, TX, USA Department of Surgery, Scott and White Memorial Hospital and Clinic, Temple, TX, USA
Xiaobo Cao
Affiliation:
Texas A&M Health Science Center College of Medicine, Temple, TX, USA Department of Surgery, Scott and White Memorial Hospital and Clinic, Temple, TX, USA
James E. Littlejohn
Affiliation:
Department of Anesthesiology, New York-Presbyterian/Weill Cornell Medical Center, New York, NY, USA
W. Roy Smythe
Affiliation:
Texas A&M Health Science Center College of Medicine, Temple, TX, USA Department of Surgery, Scott and White Memorial Hospital and Clinic, Temple, TX, USA
*
*Corresponding author: Philip A. Rascoe, Department of Surgery, Scott and White Memorial Hospital and Clinic, 7th Floor, Brindley Circle, 2401 South 31st Street, Temple, TX 76508, USA. E-mail: prascoe@swmail.sw.org
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Abstract

Malignant mesothelioma is a rare, highly aggressive cancer arising from mesothelial cells that line the pleural cavities. Approximately 80% of mesothelioma cases can be directly attributed to asbestos exposure. Additional suspected causes or co-carcinogens include other mineral fibres, simian virus 40 (SV40) and radiation. A mesothelioma epidemic in Turkey has demonstrated a probable genetic predisposition to mineral fibre carcinogenesis and studies of human tissues and animal models of mesothelioma have demonstrated genetic and epigenetic events that contribute to the multistep process of mineral fibre carcinogenesis. Several growth factors and their receptors have a significant role in the oncogenesis, progression and resistance to therapy of mesothelioma. Epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF) have been shown as targets for therapy based on promising preclinical data. However, clinical trials of tyrosine kinase inhibitors in mesothelioma have been disappointing. Bcl-XL is an important antiapoptotic member of the Bcl-2 family and is overexpressed in several solid tumours, including mesothelioma. Reduction of Bcl-XL expression in mesothelioma induces apoptosis and engenders sensitisation to cytotoxic chemotherapeutic agents. Pharmacological inhibitors of antiapoptotic Bcl-2 family members continue to undergo refinement and have shown promise in mesothelioma.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 14 , March 2012 , e12
Copyright
Copyright © Cambridge University Press 2012

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