Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma - A Review

Our plain-English summary of Preclinical Models and Resources to Facilitate Basic Science Research on Malignant Mesothelioma - A Review, by B.W. Johnson, K. Takahashi, Y.Y. Cheng (Frontiers in Oncology, 2021).

The study

• Authors: B.W. Johnson, K. Takahashi, Y.Y. Cheng
• Journal: Frontiers in Oncology
• Published: 2021;11:748444
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is an aggressive cancer with poor prognosis, predominantly caused by human occupational exposure to asbestos. The global incidence of mesothelioma is predicted to increase as a consequence of continued exposure to asbestos from a variety of sources, including construction material produced in the past in developed countries, as well as those currently being produced in developing countries. Mesothelioma typically develops after a long latency period and consequently it is often diagnosed in the clinic at an advanced stage, at which point standard care of treatment, such as chemo- and radio-therapy, are largely ineffective. Much of our current understanding of mesothelioma biology, particularly in relation to disease pathogenesis, diagnosis and treatment, can be attributed to decades of preclinical basic science research. Given the postulated rising incidence in mesothelioma cases and the limitations of current diagnostic and treatment options, continued preclinical research into mesothelioma is urgently needed. The ever-evolving landscape of preclinical models and laboratory technology available to researchers have made it possible to study human disease with greater precision and at an accelerated rate. In this review article we provide an overview of the various resources that can be exploited to facilitate an enhanced understanding of mesothelioma biology and their applications to research aimed to improve the diagnosis and treatment of mesothelioma. These resources include cell lines, animal models, mesothelioma-specific biobanks and modern laboratory techniques/technologies. Given that different preclinical models and laboratory technologies have varying limitations and applications, they must be selected carefully with respect to the intended objectives of the experiments. This review therefore aims to provide a comprehensive overview of the various preclinical models and technologies with respect to their advantages and limitations. Finally, we will detail about a highly valuable preclinical laboratory resource to curate high quality mesothelioma biospecimens for research; the biobank. Collectively, these resources are essential to the continued advancement of precision medicine to curtail the increasing health burden caused by malignant mesothelioma.

Copyright © 2021 Johnson, Takahashi and Cheng.

In plain English

This was a narrative review and did not report new experiments. The authors described laboratory resources for studying malignant mesothelioma: human and mouse cell lines, eight types of rodent models, human tissue and fluid samples, techniques such as three-dimensional cell culture, gene sequencing and droplet digital PCR, and mesothelioma biobanks. For animal models, they summarised earlier studies in which asbestos fibres were inhaled or injected. They wrote that inhalation better reflects human exposure but is costly and harder to control, while injection suits studies of what happens after exposure. They described four mesothelioma biobanks in the UK, Italy and Australia. These included the biobank of the Asbestos Diseases Research Institute in Sydney, the authors' own institute, which held over 2,000 patient-derived biospecimens. The authors concluded that no model is perfect and that models should be chosen to fit each study's aims. They wrote that immunotherapy studies need mouse models with an intact immune system. They also advocated setting up mesothelioma biobanks in developing countries that still use asbestos.

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
• Who was studied: Published work on laboratory (preclinical) models and techniques for malignant mesothelioma research, and selected mesothelioma-specific biobanks worldwide; no human or animal subjects were studied directly
• Exposure: In the animal models reviewed, asbestos fibres given to mice and rats by inhalation or injection (pleural or peritoneal); the review did not study human exposure
• Main results:
  • The review described eight types of rodent models for mesothelioma research.
  • The authors wrote that an inhalation model is probably most appropriate for studying how cancer-causing different airborne asbestos fibres are, and that an injection model suits studies of biological processes after exposure.
  • Citing earlier studies, the review reported that injection of asbestos fibres into the abdominal (peritoneal) cavity produced mesothelioma in more than 20% of wild type mice.
  • Citing an earlier study by Robinson et al., the review reported that MexTAg mice treated with gemcitabine had a median survival of 48 weeks, compared with 33 weeks for untreated controls.
  • The CREST biorepository in Genoa, Italy was reported to have biospecimens from 1,857 subjects: 454 with lung cancer, 245 with mesothelioma, 130 with other cancers and 1,028 healthy controls.
  • The ADRI biobank in Sydney was reported to hold over 2,000 mesothelioma patient-derived biospecimens and over 12,000 derivatives.
  • Citing the authors' own earlier study, the review reported that detecting homozygous loss of the CDKN2A gene by droplet digital PCR agreed with the standard FISH test in 92% of cases.
  • The authors advocated setting up mesothelioma biobanks in developing countries that continue to use asbestos.
• The authors' conclusion: The authors concluded that every model has its own advantages and disadvantages, that none is perfect, and that the reliability of results depends on choosing a model suited to the study's aims. They added that immunotherapy studies should use models with an intact immune system.

Topics

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Prognosis, Occupational Exposure, Mesothelioma, Latency.

Related studies

• Progress of malignant mesothelioma research in basic science: A review of the 14th international conference of the international mesothelioma interest group (iMig2018) — L. Wu, I. Dell'Anno, et al. (2019)
• Storylines of research on resource extraction and health in Canada: A modified metanarrative synthesis — B. Brisbois, D. Hoogeveen, et al. (2021)
• The Philadelphia pulmonary neoplasm research project: basic risk factors of lung cancer in older men — K.R. Boucot, W. Weiss, et al. (1972)
• Autophagy facilitates the release of immunogenic signals following chemotherapy in 3D models of mesothelioma — C. Follo, Y. Cheng, et al. (2019)
• Inhibition of ornithine decarboxylase 1 facilitates pegylated arginase treatment in lung adenocarcinoma xenograft models — S.K. Lam, K.P. U, et al. (2018)
• Science or public relations? The inside story of the Asbestosis Research Council, 1957-1990 — G. Tweedale (2000)

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