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

Our plain-English summary of Pleural mesothelioma (PMe): The evolving molecular knowledge of a rare and aggressive cancer, by M. Rigon, L. Mutti, M. Campanella (Molecular Oncology, 2024).

The study

• Authors: M. Rigon, L. Mutti, M. Campanella
• Journal: Molecular Oncology
• Published: 2024;18(4):797-814
• Type of article: Review
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf ofFederation of European Biochemical Societies.

In plain English

This article was a narrative review, not an original study. It summarized published research on pleural mesothelioma, the most common form of mesothelioma. It covered how asbestos is thought to cause the disease, genetic and signalling changes in tumour cells, diagnostic markers, and treatments. The authors described four main hypotheses for how asbestos fibres may lead to the cancer, including production of reactive oxygen species and fibres interfering with cell division. Citing other work, they reported that about 80% of people who develop pleural mesothelioma had previous asbestos exposure, while fewer than 5% of asbestos workers develop it, suggesting a role for genetic traits. They gave particular attention to the BAP1 gene. Its loss is linked to tumour development, yet cited studies found that patients carrying inherited (germline) BAP1 mutations had improved survival. They noted that there is no cure and most treatment is palliative. The authors concluded that knowledge of the disease's genetics and molecular mechanisms has not yet led to treatment protocols or predictive biomarker strategies, and that signalling and metabolism remain understudied.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published literature (no original data)
• Who was studied: No study population; the review drew on published research on pleural mesothelioma, covering mechanisms of carcinogenesis, signalling pathways, genetic determinants, diagnostics and treatments
• Exposure: Asbestos in general, described as the main risk factor for pleural mesothelioma. The review also mentioned genetic background and simian virus (SV40) as considered triggers. It noted that chrysotile is the most common type of asbestos produced.
• Main results:
  • The review described four main hypotheses for how asbestos causes mesothelioma: reactive oxygen species, fibres interfering with cell division, fibres carrying other hazardous molecules on their surface, and release of cytokines and growth factors.
  • Citing earlier work, the review reported that about 80% of people developing pleural mesothelioma had prior asbestos exposure, while fewer than 5% of asbestos workers develop it.
  • The review identified the CDKN2A, NF2 and BAP1 gene regions as the most frequently altered in mesothelioma, according to prior studies.
  • The review reported, from cited studies, that pleural mesothelioma patients carrying germline BAP1 mutations showed improved survival and better prognosis. Their tumours were almost exclusively of the epithelioid subtype.
  • The review stated that there is no cure and that most current treatment is palliative. It cited a 5-year survival rate after diagnosis of around 10%.
• The authors' conclusion: The authors concluded that advances in understanding the genetic and molecular mechanisms of pleural mesothelioma have not yet produced therapeutic protocols or predictive biomarker strategies. They also concluded that signalling and metabolism remain understudied.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelioma, Peritoneum, Inflammation, Pleura, Palliative Care, BAP1.

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