Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights

Our plain-English summary of Molecular Pathways in Peritoneal Mesothelioma: A Minireview of New Insights, by F. Fortarezza, F. Pezzuto, A. Marzullo, et al (Frontiers in Oncology, 2022).

The study

• Authors: F. Fortarezza, F. Pezzuto, A. Marzullo, D. Cavone, D.E. Romano, A. d'Amati, G. Serio, L. Vimercati
• Journal: Frontiers in Oncology
• Published: 2022;12:823839
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma is a rare malignant neoplasm with poor survival. It mainly affects the pleura (90%) but can arise in all serous cavities: peritoneum (5-10%), pericardium and tunica vaginalis testis (<1%). The onset of pleural mesothelioma is strictly related to asbestos exposure with a long latency time. The causal link with asbestos has also been suggested for peritoneal mesothelioma, while the importance of exposure in the onset of pericardial and tunica vaginalis testis mesotheliomas is not well known. Mesothelioma remains an aggressive and fatal disease with a five-year mortality rate higher than 95%. However, new therapeutic approaches based on molecular-targeted and immunomodulatory therapies are being explored but have conflicting results. In this context, the identification of critical targets appears mandatory. Awareness of the molecular and physiological changes leading to the neoplastic degeneration of mesothelial cells and the identification of gene mutations, epigenetic alterations, gene expression profiles and altered pathways could be helpful for selecting targetable mechanisms and molecules. In this review, we aimed to report recent research in the last 20 years focusing on the molecular pathways and prognostic factors in peritoneal mesothelioma and their possible diagnostic and therapeutic implications.

Copyright © 2022 Fortarezza, Pezzuto, Marzullo, Cavone, Romano, d’Amati, Serio and Vimercati.

In plain English

This article is a minireview, not an original study. The authors searched the Medline database using the terms "peritoneal mesothelioma" and "molecular" and listed research studies and case reports with molecular analyses of peritoneal mesothelioma. The review notes that asbestos exposure is found in about 33-50% of peritoneal cases, compared with over 90% of pleural cases. The cited studies described more frequent BAP1 alterations, and less frequent CDKN2A and NF2 alterations, in peritoneal than in pleural mesothelioma. One study (Leblay et al.) reported better overall survival in patients with BAP1 alterations. Another (Hung et al.) found ALK rearrangements in 3% of patients, mostly young women. Another (Kalra et al.) reported no EGFR mutations of the kind that would respond to targeted drugs. One group reported germline mutations in cancer susceptibility genes, especially in patients with peritoneal mesothelioma, no asbestos exposure, a second cancer, or young age. Discussing treatments explored in pleural mesothelioma, the review noted that PARP and EZH2 inhibitors tested in BAP1-negative tumours gave disappointing results. The authors concluded that recent studies show varied alterations, mostly involving BAP1 and other DNA repair, chromatin and cell cycle regulators.

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: Minireview (literature review) of published molecular studies and case reports on peritoneal mesothelioma, identified through a Medline search
• Who was studied: Published research studies and case reports in which molecular analyses of peritoneal mesothelioma were performed, listed in two tables
• Exposure: Not an exposure study. It focuses on molecular alterations. As background, the review states that asbestos exposure is found in about 33-50% of peritoneal mesothelioma cases, compared with over 90% of pleural mesothelioma cases.
• Main results:
  • In the cited studies, peritoneal mesothelioma showed a higher frequency of BAP1 alterations and a lower frequency of CDKN2A and NF2 alterations than the pleural form.
  • Leblay et al. (a reviewed study) found better overall survival in peritoneal mesothelioma patients with BAP1 mutations, loss of BAP1 protein expression, or at least one of these alterations.
  • Hung et al. (a reviewed study) detected ALK rearrangements in 3% of peritoneal mesothelioma patients, mostly young women.
  • Foster et al. had reported EGFR mutations in a high percentage of patients. A later cited study (Kalra et al.) reported that peritoneal mesothelioma does not carry somatic EGFR tyrosine kinase domain mutations that would make it sensitive to targeted therapy.
  • One cited group (Panou et al.) reported that patients with mesothelioma carry germline mutations in cancer susceptibility genes. This was especially so for those with peritoneal mesothelioma, no asbestos exposure, a second cancer diagnosis, and young age.
  • In its discussion of treatment strategies explored in pleural mesothelioma, the review notes that PARP and EZH2 inhibitors investigated in BAP1-negative tumours gave disappointing results. It does not report these results specifically for peritoneal mesothelioma.
• The authors' conclusion: The authors concluded that recently published studies show heterogeneous molecular alterations in peritoneal mesothelioma, mostly involving BAP1 and other DNA repair, chromatin and cell cycle regulators.
• Limitations the authors state:
  • The authors note that for peritoneal mesothelioma, most knowledge on treatment is extrapolated from pleural mesothelioma.

Topics

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Mesothelioma, Neoplasm, Pleura, Serous Cavities, Peritoneum, Pericardium, Tunica Vaginalis.

Related studies

• Peritoneal Mesothelioma with Residential Asbestos Exposure. Report of a Case with Long Survival (Seventeen Years) Analyzed by Cgh-Array — G. Serio, F. Pezzuto, et al. (2017)
• Mesothelioma and Colorectal Cancer: Report of Four Cases with Synchronous and Metachronous Presentation — G. Serio, F. Pezzuto, et al. (2022)
• The hippo pathway provides novel insights into lung cancer and mesothelioma treatment — X.L. Liu, R. Zuo, et al. (2018)
• New insights into the molecular pathogenesis of intrahepatic cholangiocarcinoma — T. Patel (2014)
• New insight into the molecular mechanisms of the biological effects of DNA minor groove binders — X. Zhang, S.C. Zhang, et al. (2011)
• Establishment and characterization of CRISPR/Cas9-mediated NF2-/- human mesothelial cell line: Molecular insight into fibroblast growth factor receptor 2 in malignant pleural mesothelioma — M. Wahiduzzaman, S. Karnan, et al. (2019)

Browse more research in Frontiers in Oncology, or return to medical research.