Molecular targets in malignant pleural mesothelioma treatment.
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.
Pasello
Giulia
G
U.O. Oncologia Medica, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy.
Favaretto
Adolfo
A
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000037:antagonists & inhibitors; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008654:Mesothelioma / Q000188:drug therapy*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D010997:Pleural Neoplasms / Q000188:drug therapy*; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D056572:Histone Deacetylase Inhibitors; D018970:Insulin-Like Growth Factor Binding Protein 1; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D046988:Proteasome Endopeptidase Complex