Pleural mesothelioma (PMe): The evolving molecular knowledge of a rare and aggressive cancer

Abstract

Mesothelioma is a type of late‐onset cancer that develops in cells covering the outer surface of organs. Although it can affect the peritoneum, heart, or testicles, it mainly targets the lining of the lungs, making pleural mesothelioma (PMe) the most common and widely studied mesothelioma type. PMe is caused by exposure to fibres of asbestos, which when inhaled leads to inflammation and scarring of the pleura. Despite the ban on asbestos by most Western countries, the incidence of PMe is on the rise, also facilitated by a lack of specific symptomatology and diagnostic methods. Therapeutic options are also limited to mainly palliative care, making this disease untreatable. Here we present an overview of biological aspects underlying PMe by listing genetic and molecular mechanisms behind its onset, aggressive nature, and fast‐paced progression. To this end, we report on the role of deubiquitinase BRCA1‐associated protein‐1 (BAP1), a tumour suppressor gene with a widely acknowledged role in the corrupted signalling and metabolism of PMe. This review aims to enhance our understanding of this devastating malignancy and propel efforts for its investigation.

Global burden of mesothelioma attributable to occupational asbestos exposure in 204 countries and territories: 1990–2019

“…Malignant mesothelioma is a rare and aggressive cancer that can be divided into three distinct histological subtypes: epithelioid, sarcomatoid, and biphasic (Franklin et al 2016 ). One study revealed 13 gene mutations associated with mesothelioma pathogenesis, including BAP1 (Rigon et al 2024 ) and BRCA2 (Khan et al 2024 ). Malignant mesothelioma suffers from limited therapeutic options (Hu et al 2021 ) and a poor prognosis (Schulte and Husain 2024 ) due to long latency (Zhang et al 2021 ) and a propensity for treatment resistance (Han et al 2023 ).…”