Resumen
Malignant pleural mesothelioma (MPM) is an incurable and aggressive malignancy mainly caused by exposure to asbestos fibers. Survival outcomes following the standard of care treatment, including chemotherapy and surgery, remain dismal. Targeted treatments are shortcomings for MPM, as this tumor is driven primarily by a loss of tumor suppressor genes. In this study, we explored the importance of proteins that have been shown to be dysregulated in MPM as a consequence of tumor suppressor gene loss, CUL4A and CUL4B. We assessed their expression levels and identified their correlation with clinical outcomes of MPM. We also aimed to test the efficacy and mechanisms of the available treatments that target these proteins, pevonedistat using in vitro and in vivo models. Our data suggested that CUL4B might serve as a treatment target for MPM and revealed novel mechanism of pevonedistat in the MPM tumor microenvironment. This data may be useful for understanding its efficacy in patients from clinical trials.