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.
Highlights
Malignant mesothelioma (MM) is an incurable and highly aggressive form of cancer associated with occupational or environmental exposure to asbestos; a long-established human carcinogen [1]
We further demonstrated the utility of the Droplet digital PCR (ddPCR) technique for MM biospecimen-derived biomarker detection using a large cohort of MM tissue samples, whereby co-deletion of the cyclin-dependent kinase inhibitor 2A (CDKN2A) and methylthioadenosine phosphorylase (MTAP) genes were detected via ddPCR
Mesothelioma continues to represent a significant burden on public health worldwide and its incidence is unlikely to decrease in the coming years given the long latency associated with its pathogenesis in asbestos-exposed individuals, combined with continued human exposure to asbestos fibres in the environment
Summary
Malignant mesothelioma (MM) is an incurable and highly aggressive form of cancer associated with occupational or environmental exposure to asbestos; a long-established human carcinogen [1]. Types of human MM biospecimens include pleural, pericardial and peritoneal tumour tissue biopsy samples; as well as matched whole blood, plasma, serum, pleural effusion specimens and lymphocytes In addition to their usefulness for the generation of primary cell cultures and transplantation into mouse models, human biospecimens are highly useful for biomarker validation research aimed to identify novel biomarkers to facilitate an understanding of cancer aetiology. Such knowledge can be applied to the design and development of improved MMspecific diagnostic techniques and targeted therapies to provide an accurate diagnosis and improved prognosis for patients with MM. The Ion Torrent platform in particular was utilised in a study by Sneddon et al to perform whole exome and TABLE 2 | Summary of the applications of in vitro 2D and 3D cell culture methods for MM research and their main advantages and disadvantages
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