Nat Rev Dis Primers. 2025 Aug 07. 11(1): 56
Mesothelioma is a lethal cancer caused by exposure to asbestos, which arises predominantly in the pleural lining of the thoracic cavity or, less commonly, in the peritoneum, pericardium or tunica vaginalis. The incidence of mesothelioma increased globally during the late twentieth century, correlating with the use of asbestos, and it continues to rise in some regions. Asbestos tumorigenesis involves fibre persistence that leads to DNA damage mediated by chronic inflammation. The genomic landscape of mesothelioma is predominantly characterized by tumour suppressor alterations, most frequently occurring in BAP1, CDKN2A, CDKN2B, MTAP, NF2 and TP53. Patients with mesothelioma commonly present with fatigue, dyspnoea and/or cough caused by pleural effusion, pain and reduced appetite with weight loss. Imaging, cytology, histology and immunohistochemistry are used in diagnosis and support tumour staging. Genetic tests are relevant to reveal disease predispositions. Mesotheliomas are classified on the basis of histology into three distinct subtypes: epithelioid (the most common subtype with the best prognosis), biphasic and sarcomatoid (worst prognosis). Chemotherapy has been the standard of care for the past two decades but immune checkpoint inhibition targeting PD1 and CTLA4 is now considered to be the first-line treatment, showing improvement compared with chemotherapy. Few randomized trials have investigated the role of surgery and radiotherapy and none has found a clear benefit over systemic therapies. Mesothelioma is associated with considerable negative effects on quality of life in physical and emotional domains and also substantially affects patients' families and caregivers.