The Genes-Stemness-Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints

Our plain-English summary of The Genes-Stemness-Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints, by G.M. Stella, C. Marchiò, E. Bari, et al (International Journal of Molecular Sciences, 2023).

The study

• Authors: G.M. Stella, C. Marchiò, E. Bari, I. Ferrarotti, F.R. Bertuccio, A. Di Gennaro, D.M. Abbott, P. Putignano, I. Campo, M.L. Torre, A.G. Corsico
• Journal: International Journal of Molecular Sciences
• Published: 2023;24(4)
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

MPM has a uniquely poor somatic mutational landscape, mainly driven by environmental selective pressure. This feature has dramatically limited the development of effective treatment. However, genomic events are known to be associated with MPM progression, and specific genetic signatures emerge from the exceptional crosstalk between neoplastic cells and matrix components, among which one main area of focus is hypoxia. Here we discuss the novel therapeutic strategies focused on the exploitation of MPM genetic asset and its interconnection with the surrounding hypoxic microenvironment as well as transcript products and microvesicles representing both an insight into the pathogenesis and promising actionable targets.

In plain English

This article was a review, not a new study. The authors discussed published research on malignant pleural mesothelioma (MPM), a cancer arising from the pleural mesothelium that they described as highly linked to asbestos exposure. The article did not describe how the literature was searched or selected, and it did not name specific asbestos fiber types. It covered four topics: gene changes in MPM, low-oxygen conditions (hypoxia) around the tumor, cancer stem cells, and molecules and small particles released by cells (extracellular vesicles). The review reported several findings from earlier studies. A genomic analysis confirmed BAP1, CDKN2A, CDKN2B and NF2 as the genes most often mutated. High tumor mutational burden was reported in only 5% of cases. Patients with MPM from the inherited BAP1-related cancer syndrome seemed to have a better prognosis. The COMMAND-A trial of the drug defactinib did not show a benefit in overall or progression-free survival. The authors concluded that the interplay between the tumor and its surroundings is becoming a promising treatment target. They noted that publications on extracellular vesicles in MPM were limited in number and that larger validation studies are needed.

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: Review of published literature (no methods for searching or selecting studies are described)
• Who was studied: No study population; the review covers published research on malignant pleural mesothelioma (MPM)
• Exposure: No exposure was studied. The review describes asbestos as the main trigger of MPM and does not name specific fiber types. It focuses on genetic changes, hypoxia, cancer stem cells and extracellular vesicles.
• Main results:
  • From the cited literature: the first comprehensive genomic analysis of MPM confirmed BAP1, CDKN2A and CDKN2B, and NF2 as the most frequently mutated genes. The article prints the middle gene symbols as 'CDKNA2A/B' in this passage; its Table 1 gives them as CDKN2A and CDKN2B.
  • From the cited literature: MPM showed an overall poorly mutated landscape, with high tumor mutational burden in only 5% of cases
  • From the cited literature: patients with MPM due to the inherited BAP1-related cancer syndrome seem to have a better prognosis
  • From the cited literature: variants in three iron-metabolism genes (ferritin, transferrin and hephaestin) were reported to be significantly associated with protection against developing MPM
  • From the cited literature: the level of HIF1alpha, a hypoxia marker, seems not to predict patient survival in MPM
  • From the cited literature: the phase II COMMAND-A trial did not show a benefit of defactinib on overall survival or progression-free survival in MPM
  • From the cited literature: the MESOMIR 1 phase I trial of miR-16-based TargomiRs showed a safe profile and some therapeutic activity in MPM
  • From the cited literature: Munson and colleagues found that asbestos-exposed lung epithelial cells and macrophages secrete extracellular vesicles with unique protein cargo
• The authors' conclusion: The authors concluded that the tumor and microenvironment cross-talk characteristic of MPM is becoming a promising therapeutic target. They saw hypoxia, microRNAs and extracellular vesicles as possible lines of therapy.
• Limitations the authors state:
  • The authors noted that publications suggesting a role for extracellular vesicles in MPM are limited in number
  • The authors noted that promising results on extracellular vesicles as diagnostic tools need further validation in larger samples

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, Hypoxia.

Related studies

• Adsorption of human serum albumin on the chrysotile surface: a molecular dynamics and spectroscopic investigation — R. Artali, A. Del Pra, et al. (2008)
• Interplay between inflammation and cancer — R. Khandia, A. Munjal (2020)
• Osteosarcoma pleural effusion: A diagnostic challenge with some cytologic hints — B. AbdullGaffar (2021)
• Precision immunotherapy; dynamics in the cellular profile of pleural effusions in malignant mesothelioma patients — L.A. Lievense, K. Bezemer, et al. (2017)
• Decoding the role of mesothelin in tumor dynamics and targeted treatment innovations — R. Silvestri, E. Colucci, et al. (2025)
• The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms — L.V. de Assis, M.C. Isoldi (2014)

Browse more research in International Journal of Molecular Sciences, or return to medical research.