Progress of malignant mesothelioma research in basic science: A review of the 14th international conference of the international mesothelioma interest group (iMig2018)

Our plain-English summary of Progress of malignant mesothelioma research in basic science: A review of the 14th international conference of the international mesothelioma interest group (iMig2018), by L. Wu, I. Dell'Anno, M. Lapidot, et al (Lung Cancer, 2019).

The study

• Authors: L. Wu, I. Dell'Anno, M. Lapidot, Y. Sekido, M.L. Chan, M. Kohno, V. Serre-Beinier, E. Felley-Bosco, M. de Perrot
• Journal: Lung Cancer
• Published: 2019;127:138-145
• Type of article: Review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Here we summarize the most recent update of mesothelioma research in basic science presented at the 14th iMig2018 international conference. The symposium of basic science track mainly focused on the drivers of mesothelioma initiation and progression, molecular pathogenesis, and perspectives on potential therapeutic approaches. This review covers several promising fields including strategies efficiently inhibiting YAP/TAZ functions or their critical downstream targets, heparanase inhibitors, RAN depletion, and MIF/CD74 inhibitors that may be developed as novel therapeutic approaches. In addition, targeting mesothelioma stem cells by depleting M2-polarized macrophages in tumor microenvironment or blocking Tnfsf18 (GITRL)-GITR signalling might be translated into therapeutic modalities in mesothelioma treatment.

Copyright © 2018 Elsevier B.V. All rights reserved.

In plain English

This article was a review, not a single study. The authors summarized laboratory research presented in the basic science sessions of the 14th conference of the International Mesothelioma Interest Group, held in Ottawa, Canada, in May 2018. Most work used mice and cell lines. In one study, genetically altered (Nf2+/-) mice were injected eight times with asbestos fibers into the abdomen, and mesothelioma developed in 10% of them. In another, using MexTAg mice, disease appeared significantly sooner after amphibole exposure, and erionite produced less disease. In biopsies from 68 patients with mesothelioma, a heparanase score above 90 was associated with reduced survival (hazard ratio 1.89, 95% confidence interval 1.09 to 3.27). In mice, heparanase inhibitors increased survival compared with cisplatin. Removing certain immune cells (macrophages) reduced the formation of tumor clusters in mice. Some results were described as preliminary. The authors concluded that heparanase inhibitors, RAN as a target and MIF/CD74 inhibitors showed promising antitumor effect, and that targeting mesothelioma stem cells might become a new treatment.

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 summarizing basic science (laboratory) presentations at a conference. The work described was mostly mouse experiments and cell line studies, plus some patient samples.
• Who was studied: Basic science presentations at the 14th International Mesothelioma Interest Group conference (iMig2018), Ottawa, Canada, May 2018. The work presented used mice, mouse and human mesothelioma cell lines, and some patient samples.
• Exposure: In one mouse study, asbestos fibers (type not named in the review) were injected eight times, every three weeks, into the abdomen (peritoneum) of Nf2+/- mice. Another study compared amphibole and serpentine asbestos fibers and erionite in MexTAg mice. Most other presentations studied genes, proteins and drugs in mesothelioma cells rather than asbestos exposure.
• Main results:
  • In Nf2+/- mice given repeated injections of asbestos into the abdomen, mesothelioma developed in 10% of the mice.
  • In MexTAg mice, the rate of disease (reported as ARD) was similar between the asbestos-exposed groups. Disease latency was significantly shorter in mice exposed to amphibole asbestos. Erionite exposure produced significantly less disease and a longer latency.
  • In biopsies from 68 patients with mesothelioma, a heparanase H-score above 90 was associated with reduced patient survival (hazard ratio 1.89, 95% confidence interval 1.09 to 3.27, P = 0.03).
  • In mice implanted with mesothelioma cells, heparanase inhibitors significantly increased survival compared with cisplatin treatment (p = 0.0012).
  • In an orthotopic model, a human mesothelioma cell line (H2052/484) was injected into the pleural space of athymic mice. Sizable chest tumors were seen within 2 weeks in 86% of injected mice, and median survival was 31 days.
  • In mice challenged with RN5 mesothelioma cells, removing macrophages with clodronate liposomes (compared with PBS liposomes) reduced the number of tumor spheroids from 50.7 to 9.4 at 4 weeks and from 60.8 to 9.8 at 6 weeks.
  • In the human mesothelioma cell line CRL5946, a cell viability test gave a value of 0.54 with cisplatin alone versus 0.47 with cisplatin plus GITR blocking (n = 6 per group, p = 0.014).
  • In mesothelioma cell lines, silencing the RAN gene caused a statistically significant decrease in proliferation rate eight days after treatment in all MPM cell lines, for both siRNAs.
• The authors' conclusion: The authors concluded that heparanase inhibitors, RAN as an anti-cancer target and MIF/CD74 inhibitors have shown promising antitumor effect. They added that targeting mesothelioma stem cells, by depleting M2-polarized macrophages or blocking GITRL-GITR signalling, might become new therapeutic options.
• Limitations the authors state:
  • The RAN gene silencing results were described as preliminary.
  • The MIF/CD74 inhibitor results in the xenograft model were described as preliminary.

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: Malignant Mesothelioma, Mesothelioma, STEM, Macrophage, Tumor Microenvironment.

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