Figure 1.

Potential therapeutic targets and biomarkers in the mesothelioma. Asbestos fibers, alone or with other cofactors, such as viral infection or genetic predisposition, may cause mutagenic changes resulting in the alterations of oncogenes and tumor suppressor genes leading to the transformation of normal mesothelial cells. In addition, following necrosis caused by asbestos exposure, HMGB1 primarily located in the nucleus, translocates to the cytosol and extracellular space, triggering the inflammatory response and TNF-α secretion, both by mesothelial cells and macrophages, further contributing to mesothelial cells transformation. All these events may contribute to the activation of the Notch signaling. Targeting Notch, as it is already been pursued with VEGFR and EGFR, could help to stop the progression of mesothelioma. Mesothelioma is also accompanied by changes in microRNA (miRNA) expression in cancer cells and, consequently, in biological fluids. In particular, miRNAs (miR-197-3p, miR-1281, and miR-32-3p) could become a tool for early diagnosis of mesothelioma. In this figure, the red and green arrows represent clinical and preclinical studies, respectively, aimed to sensitize mesothelioma cells to cytotoxic treatments by targeting newly discovered pathways altered in mesothelioma. The purple arrow indicates the novel potential circulating biomarkers under study for a no invasive MPM screening. Abbreviations: VEGFR, vascular endothelial growth factor receptor; EGFR, epidermal growth factor receptor; HMGB1, high-mobility group box-1; TNF-α, tumor necrosis factor-α; MPM, malignant pleural mesothelioma.