Malignant Pleural Mesothelioma: From Pathophysiology to Innovative Actionable Targets

Our plain-English summary of Malignant Pleural Mesothelioma: From Pathophysiology to Innovative Actionable Targets, by F.R. Bertuccio, S. Montini, M.A. Fusco, et al (Cancers, 2025).

The study

• Authors: F.R. Bertuccio, S. Montini, M.A. Fusco, A. Di Gennaro, G. Sciandrone, F. Agustoni, G. Galli, C. Bortolotto, J. Saddi, G. Baietto, G. Melloni, G. D'Ambrosio, A.G. Corsico, G.M. Stella
• Journal: Cancers
• Published: 2025;17(7)
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is a rare and highly aggressive cancer which arises from mesothelial layer and primarily linked to asbestos exposure, genetic predispositions, and specific mutations. Despite current treatment modalities, including chemotherapy, antiangiogenic therapy and more recently immunotherapy, the prognosis remains dismal, with a median survival time of 6-18 months.

Objectives: The urgent need for novel therapeutic strategies has prompted research into molecular targets and precision medicine approaches. At present, many potential targets for therapeutic strategies have been identified, and emerging clinical trials are demonstrating certain clinical efficacy.

Methods: This review examines advancements in understanding PM's genetic and epigenetic landscape, signaling pathways, and promising therapeutic targets.

Results: We also discuss the results of recent clinical trials and their potential implications for future treatment paradigms.

In plain English

This article was a narrative review of published research on pleural mesothelioma, a cancer of the lining of the chest. The authors work at the University of Pavia and the IRCCS Policlinico San Matteo in Pavia, Italy, and described the disease as strongly associated with asbestos exposure. The review did not present new data of its own, did not name specific asbestos fiber types, and did not say how sources were chosen. It covered proteins and signaling pathways, gene changes (BAP1, CDKN2A, NF2), microRNAs, epigenetic changes, and clinical trials of newer treatments. Citing other sources, it reported 30,618 new cases and 25,372 deaths worldwide in 2022, and a five-year survival rate below 7%. It reported that in the CheckMate 743 trial of 605 patients, median overall survival was 18.1 months with nivolumab plus ipilimumab versus 14.1 months with chemotherapy (hazard ratio 0.74; 95% CI 0.60 to 0.91). Citing earlier work, it presented as a theory the idea that NF2 mutations are not caused by asbestos-induced DNA damage or a direct inflammatory response. The authors concluded that treatment should use molecular profiling to sort patients and guide the choice of therapy.

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 research and clinical trials; no search method or study selection criteria described
• Who was studied: No study population of its own. The review drew on published laboratory, tissue and clinical trial research on pleural mesothelioma patients. The authors are based in Pavia, Italy.
• Exposure: Asbestos is named in general terms as the main cause of pleural mesothelioma. No fiber types, products, jobs or doses are studied. The review's focus is molecular targets and treatments.
• Main results:
  • Citing International Agency for Research on Cancer data, the review reported 30,618 new cases and 25,372 deaths from pleural mesothelioma worldwide in 2022.
  • The review stated that the five-year survival rate for pleural mesothelioma remains below 7%.
  • Reporting the CheckMate 743 trial (605 patients with pleural mesothelioma that could not be removed surgically), median overall survival was 18.1 months with nivolumab plus ipilimumab versus 14.1 months with chemotherapy (hazard ratio 0.74; 95% CI 0.60 to 0.91).
  • Citing other studies, the review reported gene-change frequencies in mesothelioma: inherited (germline) BAP1 mutations in 1 to 7% of malignant mesotheliomas, and CDKN2A deletion in 61 to 88% of primary pleural mesothelioma tumors. It also reported somatic NF2 mutations in 30% to 40% of pleural mesotheliomas.
  • Citing earlier work, the review presented as a theory, introduced with 'perhaps', the idea that NF2 mutations are not caused by asbestos-induced DNA damage or a direct inflammatory response. It said the lack of reports of higher mesothelioma risk among people who inherit NF2 mutations supports this theory.
  • Reporting a phase II trial of tazemetostat in patients with relapsed pleural mesothelioma and inactivated BAP1, the disease control rate was 54% at week 12 and 28% at week 24.
• The authors' conclusion: The authors concluded that improving outcomes requires a multifaceted strategy, including a personalized-medicine framework that uses molecular profiling to sort patients into groups and guide the choice of therapy.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Chemotherapy, Immunotherapy, Prognosis, Median Overall Survival, Clinical Trial.

Related studies

• Pleural Mesothelioma: Treatable Traits of a Heterogeneous Disease — F.R. Bertuccio, F. Agustoni, et al. (2023)
• BCL-XL is an actionable target for treatment of malignant pleural mesothelioma — S. Arulananda, M. O'Brien, et al. (2020)
• A3 Adenosine and P2X7 Purinergic Receptors as New Targets for an Innovative Pharmacological Therapy of Malignant Pleural Mesothelioma — F. Vincenzi, J.C. Rotondo, et al. (2021)
• Phase I Clinical Trial on Pleural Mesothelioma Using Neoadjuvant Local Administration of Paclitaxel-Loaded Mesenchymal Stromal Cells (PACLIMES Trial): Study Rationale and Design — G.M. Stella, D. Lisini, et al. (2024)
• Tumour-wide RNA splicing aberrations generate actionable public neoantigens — D.W. Kwok, N.O. Stevers, et al. (2025)
• Identification of actionable mutations in malignant pleural mesothelioma — T. Shukuya, M. Serizawa, et al. (2014)

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