Advances in the biology of malignant pleural mesothelioma

Malignant pleural mesothelioma is a highly aggressive cancer with a very poor prognosis. Although the mechanism of carcinogenesis is not fully understood, approximately 80% of malignant pleural mesothelioma can be attributed to asbestos fiber exposure. This disease is largely unresponsive to conventional chemotherapy or radiotherapy, and most patients die within 10–17 months of their first symptoms. Currently, malignant pleural mesothelioma therapy is guided by clinical stage and patient characteristics rather than by the histological or molecular features of the tumor. Several molecular pathways involved in malignant pleural mesothelioma have been identified; these include cell cycle regulation, apoptosis, growth factor pathways, and angiogenesis. Unfortunately, several agents targeting these processes, including erlotinib, gefitinib, and imatinib, have proven ineffective in clinical trials. A greater understanding of the molecular pathways involved in malignant pleural mesothelioma is needed to develop better diagnostics, therapeutics, and preventative measures. Moreover, understanding the biological basis of mesothelioma progression may facilitate personalized treatment approaches, and early identification of poor prognostic indicators may help reduce the heterogeneity of the clinical response. This paper reviews advances in the molecular biology of malignant pleural mesothelioma in terms of pathogenesis, the major molecular pathways and the associated therapeutic strategies, and the roles of biomarkers.