ASBESTOS TOXICITY STUDY IDENTIFIES POTENTIAL NOVEL TREATMENT
FOR MESOTHELIOMA AND ASBESTOSIS

Background

 

Although asbestos was phased out in Australia by the late 1980s, the long gestation period of the disease, which typically takes anything from 20-40 years to develop, means that there are around 700 new cases every year in Australia, and many more in other developed countries.

 

Asbestos-related cancers include lung cancer and malignant mesothelioma (MM) for which there is no cure.  Most patients with MM die within two years of diagnosis. Unfortunately, only about 60 out of 210 countries have banned the mining and/or use of asbestos.  Due to continued use, MM related deaths are predicted to continue to rise in industrialised and developing countries.

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Over 250 mesothelioma trials over a decade have failed, including the latest immunotherapy treatments that have had limited success with some cancers, but not MM.  Aggressive chemotherapy is only mildly successful in extending life expectancy of MM patients by an average of only 3 months.

 

Results

 

Our group based at UTS has since 2011, investigated the ability of a micronized mineral compound to counteract the toxic effects of asbestos.  At UTS, A/P George applied for and obtained grants that enabled him to design the experiments that generated the results, publications, and patents. The research team included Mr Chris McLaughlin as Research Assistant, who conducted most of the cell culture work, and Dr Xiyong Fan as Postdoctoral Fellow, who performed the mouse model trials.  Results from both cell culture and animal model studies are very promising, warranting further investigation, including the potential for a Phase I human clinical trial.

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Our pilot study, now published, found that zeolite nanoparticles reduced MM development in mouse models.  An overview of this study is given in the three figures below.  The treatments were given as injections to the peritoneal (gut) cavity of mice, as in the original published study of the effects of asbestos in this transgenic mouse strain.

 

It is well known that the leaching and ionisation of free iron from asbestos fibres generates free oxygen radicals that cause cellular damage and longer-term effects that predispose many people to asbestosis or mesothelioma.

 

By sequestering iron released from the tissue-embedded asbestos fibres, zeolite neutralises/sequesters the iron and prevents it from generating free oxygen radicals which, among other things, suppresses the immune system.  The zeolite thus allows the immune system to return to near normal and there is increased production of macrophages and clearance of asbestos nanofibres by macrophages, the first line of the immune system’s defence against foreign bodies.  Put simply, our research has shown that the immune system can be activated in such a way that asbestos fibres can be removed from tissue, which has never been demonstrated before.  We envisage that a bimodal approach to chemotherapy, using zeolite plus a cytotoxic drug, could result in more effective and more rapid tumour regression in patients suffering from mesothelioma.

Publications 

Cheng YY, Mok E, Tan S, Leygo C, McLaughlin C, George AM & Reid G (2017). SFRP tumour suppressor genes are potential plasma-based epigenetic biomarkers for malignant pleural mesothelioma. Disease Markers 2536187: 1-10.

Fan X, McLaughlin C, Ravasini J, Robinson C & George AM (2018). Zeolite protects mice from iron-induced damage in a mouse model trial. FEBS Open Bio 8: 1773-1781.

Fan X, McLaughlin C, Robinson C, Ravasini J, Schelch K, Johnson T, van Zandwijk N, Reid, G & George AM (2019). Zeolites ameliorate asbestos toxicity in a transgenic model of malignant mesothelioma. Faseb Bio Adv 1: 550-560.

Reid, G, Klebe S, van Zandwjck N & George AM (2021). Asbestos and zeolites: From A to Z via a common ion. Chem Res Toxicol. 34: 936-951.

 

Zandwijk N, Rasko JE, George AM, Frank AL & Reid G (2022). The silent mesothelioma epidemic: a call to action. Lancet Oncol. 23: 1245-1248.