Abstract
Mesothelioma is a malignancy of serosal membranes including the peritoneum, pleura, pericardium and the tunica vaginalis of the testes. Malignant mesothelioma (MM) is a rare disease with a global incidence in countries like Italy of about 1.15 per 100,000 inhabitants. Malignant Pleural Mesothelioma (MPM) is the most common form of mesothelioma, accounting for approximately 80% of disease. Although rare in the global population, mesothelioma is linked to industrial pollutants and mineral fiber exposure, with approximately 80% of cases linked to asbestos. Due to the persistent asbestos exposure in many countries, a worldwide progressive increase in MPM incidence is expected for the current and coming years. The tumor grows in a loco-regional pattern, spreading from the parietal to the visceral pleura and invading the surrounding structures that induce the clinical picture of pleural effusion, pain and dyspnea. Distant spreading and metastasis are rarely observed, and most patients die from the burden of the primary tumor. Currently, there are no effective treatments for MPM, and the prognosis is invariably poor. Some studies average the prognosis to be roughly one-year after diagnosis. The uniquely poor mutational landscape which characterizes MPM appears to derive from a selective pressure operated by the environment; thus, inflammation and immune response emerge as key players in driving MPM progression and represent promising therapeutic targets. Here we recapitulate current knowledge on MPM with focus on the emerging network between genetic asset and inflammatory microenvironment which characterize the disease as amenable target for novel therapeutic approaches.
Highlights
Malignant Pleural Mesothelioma (MPM) is an aggressive cancer with very dismal prognosis from diagnosis whose pathogenesis is mainly associated with exposure to asbestos fibers
These resistance properties have rendered the disposal of the carcinogenic asbestos-laden materials nearly impossible, posing formidable epidemiological challenges [5]
Overall High Mobility Group Box 1 protein (HMGB1) plays a crucial role in MPM onset and progression according to the following mechanisms: (i) asbestos-induced effector since its secretion by mesothelial or immune cells is highly responsive to asbestos fiber stimulation; (ii) inflammatory and epithelial-to-mesenchymal transition mediator
Summary
Malignant Pleural Mesothelioma (MPM) is an aggressive cancer with very dismal prognosis from diagnosis whose pathogenesis is mainly associated with exposure to asbestos fibers. Its temperature-resistant properties made it appealing for the insulation and heating trades [3,5]. These resistance properties have rendered the disposal of the carcinogenic asbestos-laden materials nearly impossible (fittingly, the word asbestos comes from the Greek word for “inextinguishable”), posing formidable epidemiological challenges [5]. We describe current knowledge on MPM, mainly focusing on the heterogeneous context and complex crosstalk between genetics and microenvironment that are emerging as driving force for tumor progression. A deeper understanding of these processes may allow a proper patients stratification as well as the identification of novel and effective therapeutic approaches
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