Pleural Mesothelioma: Pathogenesis, Diagnosis, Treatment, Prognosis, and Survival

ABSTRACT Pleural mesothelioma (PM) presents significant challenges in clinical management, with current treatment options such as chemotherapy, anti‐angiogenic therapies, and immunotherapies only modestly extending progression‐free survival (PFS) and overall survival (OS). Another relevant reason is the absence of subsequent‐line therapy strategies following progression of PM after approved therapy. Despite extensive research efforts, the development of effective targeted therapies has proven difficult, as most identified mutations in PM tend to be tumor suppressors rather than the driving mutations seen in other cancers. This review aims to provide an in‐depth analysis of the biological mechanisms of PM, focusing on genetic alterations, the tumor's immune microenvironment, and dysregulated signaling pathways that contribute to tumorigenesis and resistance to treatment. Additionally, we discuss the growing importance of biomarkers for patient stratification and the development of personalized therapeutic approaches tailored to individual molecular profiles. We also explore promising avenues for novel therapeutic strategies, such as combination therapies and immunotherapeutic interventions. By integrating insights from both basic and clinical research, this review seeks to present a comprehensive framework for understanding PM and advancing its therapeutic management, ultimately aiming to improve patient outcomes through more effective and targeted treatment approaches.