About this Research Topic
The carcinogenic role of inhaled asbestos fibers is well established, and we know they can lead to cancers such as lung cancer and pleural mesothelioma. For mesothelioma, asbestos exposure is the main etiological factor, contributing to more than 80% of cases, excluding tobacco consumption. In some cases of mesothelioma a germline mutation in BAP1 is present.
Therefore mesothelioma is a key cancer to study to further our understanding of the mechanisms by which asbestos leads to genotoxicity and molecular alterations. Furthermore, the well-established assays with cultured cells and animal experiments provide a knowledge of the early or short-term responses of target cells to asbestos fibers.
The development of whole-genome or whole-exome sequencing, and RNA sequencing methodologies in recent years has allowed us to build on our knowledge of the genomic characteristics of mesothelioma, especially pleural mesothelioma. Genomic studies of pleural mesothelioma first demonstrated an inter-individual tumor heterogeneity. Importantly, spatial intra-individual differences between tumors also demonstrated some heterogeneity that may define a clonal evolution of the tumor. Nevertheless, several genes have been identified to be recurrently altered, and their relevance has been tested in rodent models.
Further studies allowed a more precise characterization of the tumors, based on genetic, epigenetic and immune criteria. Molecular characteristics of pleural mesothelioma tumors appear as a continuum that transcend the classical histological features.
The landscape of epigenetic alterations that may trigger alterations of gene expression is still under investigation. In the meantime, mechanistic studies on cells in culture and in animals are mainly focused on inflammatory responses, and genotoxic effects on different mammalian cell types, including mesothelial cells.
It is now time to integrate our molecular knowledge on the asbestos-cancer relationships.
Experimental data focusing on the short-term effects of asbestos exposure have revealed genotoxic and inflammatory properties. This combined with research on the role of “mesothelioma” genes in mesothelioma development, and human molecular data has given us an insight into the critical molecular features of mesothelioma.
One challenge in the integration process is that mesothelioma can appear up to 40 years after the beginning of asbestos exposure. The data on inflammatory environment, immune landscape and clonality of the tumors, according to their molecular features, provide a timely link to achieve this goal. Moreover, asbestos has been used as model to study the biological responses of other particulate matter of concern such as carbon nanotubes, and the knowledge of their potential effect at the molecular level would be useful.
The aim of this Research Topic is to provide a molecular-based, consistent and plausible mechanism of the development of pleural mesothelioma. We are looking for submissions covering, but not limited to:
• Short-term effects of asbestos on mesothelial cells, and cells involved in the immune response;
• Genotoxicity and the role of DNA repair genes. Molecular studies (transcriptomic, epigenetic) in short-term experiments and pathway analyses
• Studies of human mesothelioma, in relation with asbestos exposure (questionnaire, lung burden…).
• The inflammatory micro-environment of mesothelioma cells
• Molecular features of mesothelioma in unexposed patients.
• Molecular features of mesothelioma in BAP1 mutated context (as BAP1 tumor predisposition syndrome is involved in some mesothelioma).
• Parallel investigations of elongated nanoparticles such as carbon nanotubes.
• Mesothelial cells in developmental biology; stem cells.
• The fate of asbestos fibers in the body following inhalation (translocation to the pleura) to determine the eventual impact of responses unrelated interactions in thoracic tissues.
Therefore mesothelioma is a key cancer to study to further our understanding of the mechanisms by which asbestos leads to genotoxicity and molecular alterations. Furthermore, the well-established assays with cultured cells and animal experiments provide a knowledge of the early or short-term responses of target cells to asbestos fibers.
The development of whole-genome or whole-exome sequencing, and RNA sequencing methodologies in recent years has allowed us to build on our knowledge of the genomic characteristics of mesothelioma, especially pleural mesothelioma. Genomic studies of pleural mesothelioma first demonstrated an inter-individual tumor heterogeneity. Importantly, spatial intra-individual differences between tumors also demonstrated some heterogeneity that may define a clonal evolution of the tumor. Nevertheless, several genes have been identified to be recurrently altered, and their relevance has been tested in rodent models.
Further studies allowed a more precise characterization of the tumors, based on genetic, epigenetic and immune criteria. Molecular characteristics of pleural mesothelioma tumors appear as a continuum that transcend the classical histological features.
The landscape of epigenetic alterations that may trigger alterations of gene expression is still under investigation. In the meantime, mechanistic studies on cells in culture and in animals are mainly focused on inflammatory responses, and genotoxic effects on different mammalian cell types, including mesothelial cells.
It is now time to integrate our molecular knowledge on the asbestos-cancer relationships.
Experimental data focusing on the short-term effects of asbestos exposure have revealed genotoxic and inflammatory properties. This combined with research on the role of “mesothelioma” genes in mesothelioma development, and human molecular data has given us an insight into the critical molecular features of mesothelioma.
One challenge in the integration process is that mesothelioma can appear up to 40 years after the beginning of asbestos exposure. The data on inflammatory environment, immune landscape and clonality of the tumors, according to their molecular features, provide a timely link to achieve this goal. Moreover, asbestos has been used as model to study the biological responses of other particulate matter of concern such as carbon nanotubes, and the knowledge of their potential effect at the molecular level would be useful.
The aim of this Research Topic is to provide a molecular-based, consistent and plausible mechanism of the development of pleural mesothelioma. We are looking for submissions covering, but not limited to:
• Short-term effects of asbestos on mesothelial cells, and cells involved in the immune response;
• Genotoxicity and the role of DNA repair genes. Molecular studies (transcriptomic, epigenetic) in short-term experiments and pathway analyses
• Studies of human mesothelioma, in relation with asbestos exposure (questionnaire, lung burden…).
• The inflammatory micro-environment of mesothelioma cells
• Molecular features of mesothelioma in unexposed patients.
• Molecular features of mesothelioma in BAP1 mutated context (as BAP1 tumor predisposition syndrome is involved in some mesothelioma).
• Parallel investigations of elongated nanoparticles such as carbon nanotubes.
• Mesothelial cells in developmental biology; stem cells.
• The fate of asbestos fibers in the body following inhalation (translocation to the pleura) to determine the eventual impact of responses unrelated interactions in thoracic tissues.
Keywords: toxicology, asbestos, mesothelioma, nanoparticles, nanotoxicology, immunotoxicology, lung cancer, genomics, integrate approach to asbestos oncogenesis
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