Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556


Molecular Targets in Malignant Pleural Mesothelioma Treatment

Author(s): Giulia Pasello, Adolfo Favaretto.


Malignant mesothelioma is an aggressive tumour of the serosal surfaces with poor prognosis and increasing incidence due to widespread previous asbestos exposure. Relative chemotherapeutic and radiotherapeutic resistance makes malignant pleural mesothelioma (MPM) difficult to manage, even though encouraging results were achieved with multimodality treatment. Better knowledge of angiogenesis and molecular pathways involved in MPM seems to be the right way to define new targets for systemic treatment. Neoangiogenesis may be considered as a critical step in the development of mesothelioma. Vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) are autocrine growth factors in MPM and epidermal growth factor receptor (EGFR) appears highly expressed in this tumour. Tyrosine kinase inhibitors (TKIs) targeting growth factors like vandetanib, dasatinib, and angiogenesis inhibitors like bevacizumab, are among the most promising agents under evaluation in clinical trials. Mesothelioma is a malignancy which owes its chemoresistance to an apoptotic defect. Thus the introduction of new biologic drugs like vorinostat, bortezomib, everolimus and temsirolimus, in the treatment of MPM finds a strong rationale. This review focuses on the current target therapies and evaluates future biologic approaches for the systemic management of MPM.

Keywords: Mesothelioma, targeted therapies, apoptosis, growth factor, angiogenesis

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Article Details

Year: 2009
Page: [1235 - 1244]
Pages: 10
DOI: 10.2174/138945009789753200
Price: $58