Targeting inflammatory factors for chemoprevention and cancer interception to tackle malignant mesothelioma

Our plain-English summary of Targeting inflammatory factors for chemoprevention and cancer interception to tackle malignant mesothelioma, by J.R. Testa, Y. Kadariya, J.S. Friedberg (Oncoscience, 2024).

The study

• Authors: J.R. Testa, Y. Kadariya, J.S. Friedberg
• Journal: Oncoscience
• Published: 2024;11:53-57
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelioma is an incurable cancer of the mesothelial lining often caused by exposure to asbestos. Asbestos-induced inflammation is a significant contributing factor in the development of mesothelioma, and genetic factors also play a role in the susceptibility to this rapidly progressive and treatment-resistant malignancy. Consequently, novel approaches are urgently needed to treat mesothelioma and prevent or reduce the overall incidence of this fatal disease. In this research perspective, we review the current state of chemoprevention and cancer interception progress in asbestos-induced mesothelioma. We discuss the different preclinical mouse models used for these investigations and the inflammatory factors that may be potential targets for mesothelioma prevention. Preliminary studies with naturally occurring phytochemicals and synthetic agents are reviewed. Results of previous clinical chemoprevention trials in populations exposed to asbestos and considerations regarding future trials are also presented.

In plain English

This short research perspective was a review, not a new study. The authors reviewed attempts to prevent asbestos-related mesothelioma, or stop it early, by targeting inflammation. Plant substances such as curcumin and sulforaphane had shown activity mainly in cell culture but had not been tested as preventive agents in animals or humans. In cited studies of crocidolite-exposed people at Wittenoom, Western Australia, retinol (vitamin A) supplements gave no support for prevention, and aspirin users did not have lower mesothelioma incidence. In the authors' group's earlier experiments, the drugs anakinra and SC144 delayed mesothelioma in asbestos-exposed genetically engineered mice but did not prevent it. Median onset was 33 weeks with anakinra versus about 22.5 weeks with placebo. The authors called this mouse model quite aggressive. A cited review reported a mesothelioma risk ratio of 1.51 (95% CI 0.80 to 2.84) in asbestos-exposed people given beta-carotene plus retinol versus placebo in the CARET trial. The authors concluded that developing ways to prevent mesothelioma is a pressing unmet need.

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 (research perspective) of chemoprevention and cancer interception research in asbestos-induced mesothelioma. It covers cell culture studies, mouse experiments and human trials and cohorts; it reports no new data.
• Who was studied: No single study population. The review covered mesothelioma cell studies, preclinical mouse models, and human groups. The mouse models included the authors' own asbestos-exposed genetically engineered mice and MexTAg mice. The human groups included crocidolite-exposed workers and residents at Wittenoom, Western Australia, and the CARET trial (more than 18,300 smokers, former smokers and asbestos-exposed workers).
• Exposure: Asbestos, including crocidolite and chrysotile, plus erionite and other elongated mineral particles. The candidate preventive agents discussed were phytochemicals, dropwort extract, selenium, retinol, beta-carotene, aspirin and other NSAIDs, COX-2 inhibitors, anakinra, SC144 and sulforaphane.
• Main results:
  • Phytochemicals such as anacardic acid, apigenin, curcumin, gallic acid, quercetin, sulforaphane and ursolic acid had been reported to hold promise mainly on the basis of cell culture assays.
  • Whether any of these natural substances prevent mesothelioma was unknown, because they had not yet been tested as preventive agents in laboratory animals or humans.
  • In a cited prevention program among former crocidolite workers at Wittenoom, retinol supplements (25,000 IU/day) gave no support for a preventive effect against mesothelioma.
  • In a cited study, aspirin and BoxA (an HMGB1 inhibitor) reduced mesothelioma growth in xenograft mice and prolonged survival of the treated animals.
  • In a cited study of asbestos-exposed MexTAg mice, aspirin had a small effect on disease latency. It did not change mesothelioma incidence or survival compared with control mice.
  • In a cited cohort of 1738 crocidolite-exposed people living or working in Wittenoom, those who reported using aspirin, COX-2 inhibitors or both did not have a lower mesothelioma incidence than a control group.
  • In the authors' group's earlier experiment in asbestos-exposed Nf2+/-;Cdkn2a+/- mice, all mice eventually developed tumors. The anakinra-treated mice had a delayed median time of mesothelioma onset compared with placebo-treated mice: 33 weeks versus about 22.5 weeks (P less than 0.0001).
  • In the authors' group's earlier work, asbestos-exposed Nf2+/-;Cdkn2a+/- mice treated with SC144 survived significantly longer than vehicle-treated mice.
  • Anakinra and SC144 delayed tumor onset in these mice but did not prevent mesothelioma.
  • The authors' group was testing sulforaphane to prevent mesothelioma in asbestos-exposed Bap1+/- mice; this study was ongoing, with no results reported.
  • A cited study (Betti et al.) reported that mesothelioma patients with pathogenic germline variants in BAP1, CDKN2A or DNA repair genes had lower asbestos exposures than mesothelioma patients without such variants (P = 0.00002).
  • According to a cited review of the CARET trial, after prolonged follow-up asbestos-exposed individuals in the beta-carotene plus retinol arm had a mesothelioma risk ratio of 1.51 (95% CI 0.80 to 2.84) compared with the placebo arm.
• The authors' conclusion: The authors concluded that no preventive intervention is currently available for people at risk of mesothelioma and that developing effective prevention strategies is a pressing unmet need. They added that the many available agents and new signaling targets give reason for optimism.
• Limitations the authors state:
  • The authors said one reason their agents did not prevent mesothelioma was that the Nf2+/-;Cdkn2a+/- mouse model is quite aggressive. In retrospect, they said, a model with a mutation in only one tumor suppressor gene would have been more appropriate.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Inflammation.

Related studies

• The role of intervention studies in ascertaining the contribution of dietary factors in lung cancer. The Seattle chemoprevention trial of retinoids in asbestos-exposed workers — G.S. Omenn, G.E. Goodman, et al. (1988)
• Inflammation as a chemoprevention target in asbestos-induced malignant mesothelioma — Y. Kadariya, E. Sementino, et al. (2022)
• Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis — H. Ohshima, H. Bartsch (1994)
• Asbestos induces inflammatory cytokines in the lung through redox sensitive transcription factors — M.I. Luster, P.P. Simeonova (1998)
• Carborundum pneumoconiosis. Fibers in the mineral activate macrophages to produce fibroblast growth factors and sustain the chronic inflammatory disease — R. Bégin, A. Dufresne, et al. (1989)
• Degradation of cartilage proteoglycan and collagen by synovial cells. Stimulation by macrophages under activation by phagocytosis, lymphocyte factors, bacterial products or other inflammatory stimuli — C. Peeters-Joris, G. Vaes (1984)

Browse return to medical research.