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A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies
There is growing recognition across broad sectors of the scientific community that use of genomic biomarkers has the potential to reduce the need for conventional rodent carcinogenicity studies of industrial chemicals, agrochemicals, and pharmaceuticals through a weight-of-evidence approach. These b...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238304/ https://www.ncbi.nlm.nih.gov/pubmed/35404422 http://dx.doi.org/10.1093/toxsci/kfac041 |
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author | Corton, J Christopher Mitchell, Constance A Auerbach, Scott Bushel, Pierre Ellinger-Ziegelbauer, Heidrun Escobar, Patricia A Froetschl, Roland Harrill, Alison H Johnson, Kamin Klaunig, James E Pandiri, Arun R Podtelezhnikov, Alexei A Rager, Julia E Tanis, Keith Q van der Laan, Jan Willem Vespa, Alisa Yauk, Carole L Pettit, Syril D Sistare, Frank D |
author_facet | Corton, J Christopher Mitchell, Constance A Auerbach, Scott Bushel, Pierre Ellinger-Ziegelbauer, Heidrun Escobar, Patricia A Froetschl, Roland Harrill, Alison H Johnson, Kamin Klaunig, James E Pandiri, Arun R Podtelezhnikov, Alexei A Rager, Julia E Tanis, Keith Q van der Laan, Jan Willem Vespa, Alisa Yauk, Carole L Pettit, Syril D Sistare, Frank D |
author_sort | Corton, J Christopher |
collection | PubMed |
description | There is growing recognition across broad sectors of the scientific community that use of genomic biomarkers has the potential to reduce the need for conventional rodent carcinogenicity studies of industrial chemicals, agrochemicals, and pharmaceuticals through a weight-of-evidence approach. These biomarkers fall into 2 major categories: (1) sets of gene transcripts that can identify distinct tumorigenic mechanisms of action; and (2) cancer driver gene mutations indicative of rapidly expanding growth-advantaged clonal cell populations. This call-to-action article describes a collaborative approach launched to develop and qualify biomarker gene expression panels that measure widely accepted molecular pathways linked to tumorigenesis and their activation levels to predict tumorigenic doses of chemicals from short-term exposures. Growing evidence suggests that application of such biomarker panels in short-term exposure rodent studies can identify both tumorigenic hazard and tumorigenic activation levels for chemical-induced carcinogenicity. In the future, this approach will be expanded to include methodologies examining mutations in key cancer driver gene mutation hotspots as biomarkers of both genotoxic and nongenotoxic chemical tumor risk. Analytical, technical, and biological validation studies of these complementary genomic tools are being undertaken by multisector and multidisciplinary collaborative teams within the Health and Environmental Sciences Institute. Success from these efforts will facilitate the transition from current heavy reliance on conventional 2-year rodent carcinogenicity studies to more rapid animal- and resource-sparing approaches for mechanism-based carcinogenicity evaluation supporting internal and regulatory decision-making. |
format | Online Article Text |
id | pubmed-9238304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-92383042022-06-29 A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies Corton, J Christopher Mitchell, Constance A Auerbach, Scott Bushel, Pierre Ellinger-Ziegelbauer, Heidrun Escobar, Patricia A Froetschl, Roland Harrill, Alison H Johnson, Kamin Klaunig, James E Pandiri, Arun R Podtelezhnikov, Alexei A Rager, Julia E Tanis, Keith Q van der Laan, Jan Willem Vespa, Alisa Yauk, Carole L Pettit, Syril D Sistare, Frank D Toxicol Sci Forum There is growing recognition across broad sectors of the scientific community that use of genomic biomarkers has the potential to reduce the need for conventional rodent carcinogenicity studies of industrial chemicals, agrochemicals, and pharmaceuticals through a weight-of-evidence approach. These biomarkers fall into 2 major categories: (1) sets of gene transcripts that can identify distinct tumorigenic mechanisms of action; and (2) cancer driver gene mutations indicative of rapidly expanding growth-advantaged clonal cell populations. This call-to-action article describes a collaborative approach launched to develop and qualify biomarker gene expression panels that measure widely accepted molecular pathways linked to tumorigenesis and their activation levels to predict tumorigenic doses of chemicals from short-term exposures. Growing evidence suggests that application of such biomarker panels in short-term exposure rodent studies can identify both tumorigenic hazard and tumorigenic activation levels for chemical-induced carcinogenicity. In the future, this approach will be expanded to include methodologies examining mutations in key cancer driver gene mutation hotspots as biomarkers of both genotoxic and nongenotoxic chemical tumor risk. Analytical, technical, and biological validation studies of these complementary genomic tools are being undertaken by multisector and multidisciplinary collaborative teams within the Health and Environmental Sciences Institute. Success from these efforts will facilitate the transition from current heavy reliance on conventional 2-year rodent carcinogenicity studies to more rapid animal- and resource-sparing approaches for mechanism-based carcinogenicity evaluation supporting internal and regulatory decision-making. Oxford University Press 2022-04-11 /pmc/articles/PMC9238304/ /pubmed/35404422 http://dx.doi.org/10.1093/toxsci/kfac041 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Forum Corton, J Christopher Mitchell, Constance A Auerbach, Scott Bushel, Pierre Ellinger-Ziegelbauer, Heidrun Escobar, Patricia A Froetschl, Roland Harrill, Alison H Johnson, Kamin Klaunig, James E Pandiri, Arun R Podtelezhnikov, Alexei A Rager, Julia E Tanis, Keith Q van der Laan, Jan Willem Vespa, Alisa Yauk, Carole L Pettit, Syril D Sistare, Frank D A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies |
title | A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies |
title_full | A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies |
title_fullStr | A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies |
title_full_unstemmed | A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies |
title_short | A Collaborative Initiative to Establish Genomic Biomarkers for Assessing Tumorigenic Potential to Reduce Reliance on Conventional Rodent Carcinogenicity Studies |
title_sort | collaborative initiative to establish genomic biomarkers for assessing tumorigenic potential to reduce reliance on conventional rodent carcinogenicity studies |
topic | Forum |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238304/ https://www.ncbi.nlm.nih.gov/pubmed/35404422 http://dx.doi.org/10.1093/toxsci/kfac041 |
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