Negative results of an Italian Group for Mesothelioma (GIMe.) pilot study of single-agent imatinib mesylate in malignant pleural mesothelioma
Policlinico San Matteo Pavia Fondazione IRCCS, Ticinum, Lombardy, Italy Cancer Chemotherapy and Pharmacology
(Impact Factor: 2.77).
02/2007; 59(1):149-50. DOI: 10.1007/s00280-006-0243-4
Available from: Karim Vermaelen
- "Imatinib is a highly selective inhibitor of the bcr/abl mutated tyrosine kinase, as well as of both c-kit and PDGFRs. Several Phase II studies have been conducted with imatinib mesylate in MPM refractory to chemotherapy or chemonaive patients, but negative results were reported (Kumar-Singh et al., 1999; Millward et al., 2003; Villano et al., 2004; Mathy et al., 2005; Porta et al., 2007). In vitro and in vivo experiments demonstrated that STI-571 can cause MPM cell apoptosis and death through inhibition of the AKT/PI3K pathway and that it can also enhances MPM sensitivity to gemcitabine or pemetrexed (Bertino et al., 2007). "
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ABSTRACT: Malignant pleural mesothelioma (MPM) is a rare, aggressive tumor with a poor prognosis. In view of the poor survival benefit from first-line chemotherapy and the lack of subsequent effective treatment options, there is a strong need for the development of more effective treatment approaches for patients with MPM. This review will provide a comprehensive state of the art of new investigational approaches for mesothelioma. In an introductory section, the etiology, epidemiology, natural history, and standard of care treatment for MPM will be discussed. This review provide an update of the major clinical trials that impact mesothelioma treatment, discuss the impact of novel therapeutics, and provide perspective on where the clinical research in mesothelioma is moving. The evidence was collected by a systematic analysis of the literature (2000-2011) using the databases Medline (National Library of Medicine, USA), Embase (Elsevier, Netherlands), Cochrane Library (Great Britain), National Guideline Clearinghouse (USA), HTA Database (International Network of Agencies for Health Technology Assessment - INAHTA), NIH database (USA), International Pleural Mesothelioma Program - WHOLIS (WHO Database), with the following keywords and filters: mesothelioma, guidelines, treatment, surgery, chemotherapy, radiotherapy, review, investigational, drugs. Currently different targeted therapies and biologicals are under investigation for MPM. It is important that the molecular biologic research should first focus on mesothelioma-specific pathways and biomarkers in order to have more effective treatment options for this disease. The use of array technology will be certainly an implicit gain in the identification of new potential prognostic or biomarkers or important pathways in the MPM pathogenesis. Probably a central mesothelioma virtual tissue bank may contribute to the ultimate goal to identify druggable targets and to develop personalized treatment for the MPM patients.
Available from: PubMed Central
- "Vogelzang et al. recently reviewed new agents that under evaluation for the treatment of MM, including EGFR, PDGFR, VEGF and HGF inhibitors, inhibitors of mTOR, a downstream molecule of the PI3K/AKT pathway, and inhibitors of the proteasome/ubiquitin pathway (Vogelzang, 2005). Although recent results in clinical trials using the tyrosine kinase receptor inhibitor imatinib mesylate, which targets PDGFR and c-Kit, have not been encouraging (Mathy, 2005; Porta, 2007), it is to be hoped that the common effort of medical and research disciplines will in the future allow us to achieve more success in treating this highly lethal tumor. "
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ABSTRACT: Malignant mesothelioma (MM) is a malignant tumor derived from mesothelial cells, native cells of the body cavities. Exposure to asbestos is the most strongly established etiologic factor, predominantly for the most common disease form, pleural mesothelioma. The pathogenesis of MM involves the accumulation of extensive cytogenetic changes, as well as cancer-related phenotypic alterations that facilitate tumor cell survival, invasion and metastasis. This review presents current knowledge regarding the biological characteristics of this disease that are linked to the so-called hallmarks of cancer. In addition, data suggesting that the anatomic site (solid tumor vs. effusion) affects the expression of metastasis-associated and regulatory molecules in MM are presented. Finally, recent work in which high-throughput methodology has been applied to MM research is reviewed. The data obtained in the reviewed research may aid in defining new prognostic markers and therapeutic targets for this aggressive disease in the future.
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