The Role of Epithelial-Mesenchymal Transition in Malignant Pleural Mesothelioma: From Pathogenesis to Diagnosis and Treatment

Our plain-English summary of The Role of Epithelial-Mesenchymal Transition in Malignant Pleural Mesothelioma: From Pathogenesis to Diagnosis and Treatment, by D.E. Magouliotis, F. Minervini, U. Cioffi, et al (Cells, 2025).

The study

• Authors: D.E. Magouliotis, F. Minervini, U. Cioffi, M. De Simone, D. Patrini, M. Scarci
• Journal: Cells
• Published: 2025;14(8)
• Type of article: Review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleural lining, primarily associated with asbestos exposure. Despite advancements in multimodal treatment, patient survival remains poor. Epithelial-mesenchymal transition (EMT) has emerged as a crucial process driving MPM pathogenesis, metastasis, and resistance to therapy. This review explores the molecular mechanisms underlying EMT in MPM, including key signaling pathways such as TGF-β, Wnt/β-catenin, and PI3K/Akt. We also discuss the diagnostic and prognostic significance of EMT-related biomarkers and emerging targeted therapies aimed at reversing EMT or exploiting EMT-induced vulnerabilities. Additionally, recent clinical trials, including the MARS 2 trial, are reviewed to provide insight into the evolving treatment landscape.

In plain English

This article, labeled a Perspective and describing itself as a review, summarized published research on epithelial–mesenchymal transition (EMT) in malignant pleural mesothelioma (MPM). EMT is a process in which cells lose their attachments to neighbouring cells and become more mobile and invasive. The article reported no new patients or data and did not describe how the studies it discussed were chosen. Asbestos appeared only as background: the authors described MPM as strongly linked to asbestos exposure and did not name any fiber types. Drawing on earlier studies, the authors described signaling pathways thought to drive EMT, the role of loss of the NF2 gene, and links between EMT and resistance to chemotherapy and to immune attack. They reviewed proposed markers such as E-cadherin, vimentin, periostin, AXL and the miR-200 family, and experimental drugs aimed at EMT. They noted that trials of FAK inhibitors gave mixed results. They also discussed the CheckMate 743 and MARS 2 trials. The authors concluded that EMT is a key driver of MPM progression and that targeting EMT pathways holds promise.

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, published as a 'Perspective' article. No original data, and no description of how the literature was searched or selected.
• Who was studied: No patients or subjects were studied. The article discusses published research on malignant pleural mesothelioma (MPM).
• Exposure: Asbestos was not studied. It is mentioned only as background, as the main association of MPM, with no fiber types named. The article's subject is the biological process EMT, not an exposure.
• Main results:
  • Citing earlier studies, the review described several signaling pathways that regulate EMT in MPM, with TGF-beta presented as one of the most prominent, along with Wnt/beta-catenin and PI3K/Akt.
  • Citing earlier studies, the review described loss of NF2, one of the most frequently mutated genes in mesothelioma, as implicated in EMT regulation.
  • The review described resistance to chemotherapy (such as pemetrexed and cisplatin) as one of the major consequences of EMT in MPM.
  • The review stated that mesenchymal-like MPM cells show increased expression of PD-L1, which may help tumors evade the immune system.
  • The review discussed EMT-related biomarkers proposed for diagnosis and prognosis, including E-cadherin, vimentin, periostin, AXL and microRNAs such as the miR-200 family and miR-205.
  • The review described experimental drugs aimed at EMT. It stated that clinical trials of FAK inhibitors such as defactinib in MPM gave mixed results.
  • The review stated that AXL inhibitors are being tested in clinical trials.
  • The review described the CheckMate 743 trial as showing better survival with nivolumab plus ipilimumab than with chemotherapy in non-epithelioid MPM. The authors noted it remains unclear whether the same benefit applies to epithelioid MPM.
  • The review described the MARS 2 trial, which compared extended pleurectomy/decortication surgery plus chemotherapy with chemotherapy alone, as suggesting that surgery did not significantly improve overall survival.
• The authors' conclusion: The authors concluded that EMT is a key driver of malignant pleural mesothelioma progression, affecting invasiveness, metastasis, immune evasion and treatment resistance. They concluded that targeting EMT-related pathways holds promise for overcoming therapy resistance.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Metastasis, Biomarker, Clinical Trial, MARS 2 Trial.

Related studies

• Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway — T. Chen, H. Nie, et al. (2014)
• Multi-walled carbon nanotubes directly induce epithelial-mesenchymal transition in human bronchial epithelial cells via the TGF-β-mediated Akt/GSK-3β/SNAIL-1 signalling pathway — M. Polimeni, G.R. Gulino, et al. (2016)
• FGF2 and EGF induce epithelial-mesenchymal transition in malignant pleural mesothelioma cells via a MAPKinase/MMP1 signal — K. Schelch, C. Wagner, et al. (2018)
• Epithelial-mesenchymal transition in malignant mesothelioma — A. Fassina, R. Cappellesso, et al. (2012)
• Prognostic significance of epithelial-mesenchymal transition in malignant pleural mesothelioma — A. Schramm, I. Opitz, et al. (2010)
• The Epithelial-to-Mesenchymal Transition (EMT) in the Development and Metastasis of Malignant Pleural Mesothelioma — V. Ramundo, G. Zanirato, et al. (2021)

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