Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies

Expert Rev Respir Med. 2015 Oct;9(5):633-54. doi: 10.1586/17476348.2015.1081066. Epub 2015 Aug 26.

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.

Keywords: BAP1; HMGB1; asbestos; aspirin; carcinogenesis; immunotherapy; mesothelioma; molecular therapy; polyclonal tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Immunotherapy / methods
  • Lung Neoplasms / etiology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / physiopathology
  • Lung Neoplasms / therapy*
  • Mesothelioma / etiology
  • Mesothelioma / genetics*
  • Mesothelioma / physiopathology
  • Mesothelioma / therapy*
  • Mesothelioma, Malignant
  • Molecular Targeted Therapy* / methods
  • Peritoneal Neoplasms / etiology
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / physiopathology
  • Peritoneal Neoplasms / therapy
  • Pleural Neoplasms / etiology
  • Pleural Neoplasms / genetics*
  • Pleural Neoplasms / physiopathology
  • Pleural Neoplasms / therapy*