From biology to therapy: current standards and emerging strategies in pleural mesothelioma

Pleural mesothelioma (PM) is an aggressive malignancy with limited therapeutic options and poor long-term prognosis. Platinum-based chemotherapy has been the standard-of-care for most patients for decades. While the decoding of the genomic alterations in PM has triggered renewed interest in mesothelioma biology and targeted therapies, these have yet to reach clinical practice. The recent introduction of dual immune checkpoint blockade (ICB) with nivolumab plus ipilimumab has marked the first major advance in PM treatment for decades, yet, many patients do not respond to these drugs and durable long-term responses remain rare. A range of alternative treatment modalities are currently under clinical investigation in PM, including antibody-drug conjugates, bi-specific antibodies, chimeric antigen receptor T-cells, cancer vaccines, and oncolytic viruses. Here we review recent progress in the understanding of PM biology and evaluate relevant phase I-III clinical trials aimed at improving treatment for this disease. We also highlight ongoing and future clinical trials with promising candidates for PM therapy.