These MMe cells were tumorigenic upon intraperitoneal injection. We characterized an orthotopic model using MMe cells derived from Cdkn2a+/− Nf2+/− mice chronically injected with asbestos. Thus, an alternative model with high tumor penetrance without asbestos is urgently needed. However, most of these models require specialized breeding facilities and long-term exposure of mice to asbestos for MMe development. Several genetically engineered mouse models have been generated by introducing the same genetic lesions found in human MMe. Genomic studies have revealed that the most frequent genetic lesions in human MMe are mutations in tumor suppressor genes. The best-defined risk factor is exposure to carcinogenic mineral fibers (e.g., asbestos). Malignant mesothelioma (MMe) is a rare malignancy originating from the linings of the pleural, peritoneal and pericardial cavities. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. The long latency period of 20–40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. Approximately 80% of PM patients have a history of asbestos exposure. Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity.

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