Pleural mesothelioma: a snapshot of emerging drug targets and opportunities for non-surgical therapeutic advancement

IntroductionPleural mesothelioma is a rare and aggressive cancer originating in the pleura, with a devastating prognosis and limited treatment options. There have been significant advancements in the management of this disease in recent years. Since 2021, nivolumab and ipilimumab immune checkpoint inhibitors have become the new standard of care for first-line treatment of pleural mesothelioma.Areas coveredWhile a combination of chemotherapy and immune checkpoint inhibitors appears to be the next step, targeted therapies are emerging thanks to our understanding of the oncogenesis of pleural mesothelioma. Moreover, several new strategies are currently being investigated, including viral therapy, antibody-drug conjugates, and even cell therapies with CAR-T cells or dendritic cells. In this review, we will explore the various future opportunities that could potentially transform patients' lives in light of the clinical trials that have been conducted.Expert opinionFuture clinical studies aim to rebiopsy patients after disease progression to identify new molecular alterations and to be associated with ancillary studies, guiding subsequent therapy decisions. Predicting and investigating treatment resistance mechanisms will lead to innovative approaches and improved treatment outcomes.