Abstract
Malignant mesothelioma (MM), a rare and severe cancer, mainly caused as a result of past-asbestos exposure, is presently a public health concern. Current molecular studies aim to improve the outcome of the disease, providing efficient therapies based on the principles of precision medicine. To model the molecular profile of human malignant mesothelioma, animal models have been developed in rodents, wild type animals and genetically engineered mice harbouring mutations in tumour suppressor genes, especially selecting genes known to be inactivated in human malignant mesothelioma. Animals were either exposed or not exposed to asbestos or to other carcinogenic fibres, to understand the mechanism of action of fibres at the molecular level, and the role of the selected genes in mesothelial carcinogenesis. The aim of the manuscript was to compare mesothelioma models to human malignant mesothelioma and to specify the clue genes playing a role in mesothelial carcinogenesis. Collectively, MM models recapitulate the clinical features of human MM. At least two altered genes are needed to induce malignant mesothelioma in mice. Two pathways regulated by Cdkn2a and Trp53 seem independent key players in mesothelial carcinogenesis. Other genes and pathways appear as bona fide modulators of the neoplastic transformation.
Highlights
Human malignant mesothelioma (HMM) is a cancer with current poor outcome, which is diagnosed with advanced non-curable disease
Malignant mesotheliomas (MM) models have been generated to understand the carcinogenic mechanism induced by asbestos fibres or to identify the most relevant genes and important signalling pathways associated to mesothelial cell transformation
Important deregulation of the mitotic spindle assembly checkpoint pathway (MSAC) and microtubule network has been reported in malignant pleural mesothelioma (MPM), no mutation was detected in these genes [42]
Summary
Human malignant mesothelioma (HMM) is a cancer with current poor outcome, which is diagnosed with advanced non-curable disease. Malignant mesotheliomas (MM) models have been generated to understand the carcinogenic mechanism induced by asbestos fibres or to identify the most relevant genes and important signalling pathways associated to mesothelial cell transformation. This aim was developed with both in vitro studies on mammalian cells, including mesothelial cells, and in vivo studies in animals [3]. Recombinant inbred mouse lines were designed to determine the genetic bases of the disease In this context, genetically engineered mice (GEM) carrying genes modified to mimic the human disease were chosen and exposed or not to carcinogenic fibres.
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