Military Exposure-Related Pleural Mesothelioma: An Innovative Translational Approach to Inform Novel Molecular-Targeted Treatment Development

Malignant pleural mesothelioma (MPM) is a highly aggressive form of cancer that develops within the pleural lining of the lungs. Asbestos-related malignancies dropped precipitously in military/veteran populations upon the removal of asbestos from naval ship construction. However, older naval vessels and military facilities still containing asbestos were still in use decades later, resulting in thousands of veterans suffering asbestos exposure. Indeed, it is estimated that military veterans account for one third of all MPM patients. Despite this estimation, there is little data on the phenotype of military exposure and MPM pathogenesis. We recently defined the mutational landscape of MPM and have identified the most commonly mutated genes as BAP1, NF2, TP53, and SETD2, as well as other frequent mutations. We have also classified MPM into 4 distinct molecular clusters that provide new opportunities to identify MPM patients with better prognosis as well as to rationally divide tumors based on distinct molecular/biochemical driving mechanisms.