title: Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma.
abstract: Human malignant pleural mesothelioma (hMPM) is an aggressive asbestos-associated cancer, the incidence of which is increasing and which, despite progress in diagnosis and therapy, continues to have a poor prognosis. Asbestos fibers induce aberrant cell signaling, leading to proto-oncogene activation and chemoresistance. In this review, we discuss the evolution of pharmacological management of hMPM up to the most recent advances. Monotherapy with single cytotoxic drugs achieves modest objective response rates, seldom reaching 30%. However, combination regimens using novel drugs and standard molecules are showing gradually improving responses and clinical benefits. Phase II/III studies have identified pemetrexed, a multitarget folate pathway inhibitor in combination with platinum derivatives, and the cisplatin/gemcitabine association as front-line chemotherapy for hMPM. Detailed knowledge of molecular mechanisms of signal transduction and neoangiogenesis in hMPM should aid in the design and screening of other promising compounds such as more efficacious receptor tyrosine kinase inhibitors.
authors.affiliation: Department of Translational Oncology Research, Gene Transfer Laboratory, National Cancer Institute, Largo Rosanna Benzi, 10 16132 Genoa, Italy. roberto.favoni@istge.it
authors.forename: Roberto E
authors.initials: RE
authors.lastname: Favoni
authors.forename: Tullio
authors.initials: T
authors.lastname: Florio
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001194:Asbestos; D002945:Cisplatin / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D005971:Glutamates / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008495:Medical Oncology / Q000379:methods; D008654:Mesothelioma / Q000503:physiopathology / Q000628:therapy*; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D010166:Palliative Care; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000503:physiopathology / Q000628:therapy*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D000090063:Proto-Oncogene Mas; D011878:Radiotherapy; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; C000715470:MAS1 protein, human; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D000068437:Pemetrexed; D001194:Asbestos; D006147:Guanine; D002945:Cisplatin