Malignant Pleural Mesothelioma: From Pathophysiology to Innovative Actionable Targets

Background: Pleural mesothelioma (PM) is a rare and highly aggressive cancer which arises from mesothelial layer and primarily linked to asbestos exposure, genetic predispositions, and specific mutations. Despite current treatment modalities, including chemotherapy, antiangiogenic therapy and more recently immunotherapy, the prognosis remains dismal, with a median survival time of 6–18 months. Objectives: The urgent need for novel therapeutic strategies has prompted research into molecular targets and precision medicine approaches. At present, many potential targets for therapeutic strategies have been identified, and emerging clinical trials are demonstrating certain clinical efficacy. Methods: This review examines advancements in understanding PM’s genetic and epigenetic landscape, signaling pathways, and promising therapeutic targets. Results: We also discuss the results of recent clinical trials and their potential implications for future treatment paradigms.