Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens
With recent rapid advancement of methodological tools, mechanistic understanding of biological processes leading to carcinogenesis is expanding. New approach methodologies such as transcriptomics can inform on non-genotoxic mechanisms of chemical carcinogens and can be developed for regulatory appli...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/21/12718 |
| _version_ | 1797468060579266560 |
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| author | Yusuke Oku Federica Madia Pierre Lau Martin Paparella Timothy McGovern Mirjam Luijten Miriam N. Jacobs |
| author_facet | Yusuke Oku Federica Madia Pierre Lau Martin Paparella Timothy McGovern Mirjam Luijten Miriam N. Jacobs |
| author_sort | Yusuke Oku |
| collection | DOAJ |
| description | With recent rapid advancement of methodological tools, mechanistic understanding of biological processes leading to carcinogenesis is expanding. New approach methodologies such as transcriptomics can inform on non-genotoxic mechanisms of chemical carcinogens and can be developed for regulatory applications. The Organisation for the Economic Cooperation and Development (OECD) expert group developing an Integrated Approach to the Testing and Assessment (IATA) of Non-Genotoxic Carcinogens (NGTxC) is reviewing the possible assays to be integrated therein. In this context, we review the application of transcriptomics approaches suitable for pre-screening gene expression changes associated with phenotypic alterations that underlie the carcinogenic processes for subsequent prioritisation of downstream test methods appropriate to specific key events of non-genotoxic carcinogenesis. Using case studies, we evaluate the potential of gene expression analyses especially in relation to breast cancer, to identify the most relevant approaches that could be utilised as (pre-) screening tools, for example Gene Set Enrichment Analysis (GSEA). We also consider how to address the challenges to integrate gene panels and transcriptomic assays into the IATA, highlighting the pivotal omics markers identified for assay measurement in the IATA key events of inflammation, immune response, mitogenic signalling and cell injury. |
| first_indexed | 2024-03-09T19:02:10Z |
| format | Article |
| id | doaj.art-033f56b2441f4199aaaf0ffecffd7ef8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:02:10Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-033f56b2441f4199aaaf0ffecffd7ef82023-11-24T04:56:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211271810.3390/ijms232112718Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic CarcinogensYusuke Oku0Federica Madia1Pierre Lau2Martin Paparella3Timothy McGovern4Mirjam Luijten5Miriam N. Jacobs6The Organisation for Economic Cooperation and Development (OECD), 2 Rue Andre Pascal, 75016 Paris, FranceEuropean Commission, Joint Research Centre (JRC), Via Enrico Fermi, 2749, 21027 Ispra, ItalyIstituto Italiano di Tecnologia, 16163 Genova, ItalyInstitute of Medical Biochemistry, Biocenter, Medical University of Innsbruck, Innrain 80, 6020 Innbruck, AustriaUS Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20901, USACentre for Health Protection, National Institute for Public Health and the Environment (RIVM), Antonie van Leeuwenhoeklaan 9, Bilthoven, 3721 MA Utrecht, The NetherlandsCentre for Radiation, Chemical and Environmental Hazard (CRCE), Public Health England (PHE), Chilton OX11 0RQ, Oxfordshire, UKWith recent rapid advancement of methodological tools, mechanistic understanding of biological processes leading to carcinogenesis is expanding. New approach methodologies such as transcriptomics can inform on non-genotoxic mechanisms of chemical carcinogens and can be developed for regulatory applications. The Organisation for the Economic Cooperation and Development (OECD) expert group developing an Integrated Approach to the Testing and Assessment (IATA) of Non-Genotoxic Carcinogens (NGTxC) is reviewing the possible assays to be integrated therein. In this context, we review the application of transcriptomics approaches suitable for pre-screening gene expression changes associated with phenotypic alterations that underlie the carcinogenic processes for subsequent prioritisation of downstream test methods appropriate to specific key events of non-genotoxic carcinogenesis. Using case studies, we evaluate the potential of gene expression analyses especially in relation to breast cancer, to identify the most relevant approaches that could be utilised as (pre-) screening tools, for example Gene Set Enrichment Analysis (GSEA). We also consider how to address the challenges to integrate gene panels and transcriptomic assays into the IATA, highlighting the pivotal omics markers identified for assay measurement in the IATA key events of inflammation, immune response, mitogenic signalling and cell injury.https://www.mdpi.com/1422-0067/23/21/12718integrated approaches to testing and assessment (IATA)non-genotoxic carcinogen(s) (NGTxC(s))gene expressiontranscriptomicscarcinogenicityorganisation for economic co-operation and development (OECD) |
| spellingShingle | Yusuke Oku Federica Madia Pierre Lau Martin Paparella Timothy McGovern Mirjam Luijten Miriam N. Jacobs Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens International Journal of Molecular Sciences integrated approaches to testing and assessment (IATA) non-genotoxic carcinogen(s) (NGTxC(s)) gene expression transcriptomics carcinogenicity organisation for economic co-operation and development (OECD) |
| title | Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens |
| title_full | Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens |
| title_fullStr | Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens |
| title_full_unstemmed | Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens |
| title_short | Analyses of Transcriptomics Cell Signalling for Pre-Screening Applications in the Integrated Approach for Testing and Assessment of Non-Genotoxic Carcinogens |
| title_sort | analyses of transcriptomics cell signalling for pre screening applications in the integrated approach for testing and assessment of non genotoxic carcinogens |
| topic | integrated approaches to testing and assessment (IATA) non-genotoxic carcinogen(s) (NGTxC(s)) gene expression transcriptomics carcinogenicity organisation for economic co-operation and development (OECD) |
| url | https://www.mdpi.com/1422-0067/23/21/12718 |
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