Current Landscape of NRF2 Biomarkers in Clinical Trials
The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by <i>NFE2L2</i>) plays a critical role in the maintenance of cellular redox and metabolic homeostasis, as well as the regulation of inflammation and cellular detoxication pathways. The contribution of the NRF2 pathway to...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/8/716 |
| _version_ | 1797559566773256192 |
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| author | Yoko Yagishita Tonibelle N. Gatbonton-Schwager Melissa L. McCallum Thomas W. Kensler |
| author_facet | Yoko Yagishita Tonibelle N. Gatbonton-Schwager Melissa L. McCallum Thomas W. Kensler |
| author_sort | Yoko Yagishita |
| collection | DOAJ |
| description | The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by <i>NFE2L2</i>) plays a critical role in the maintenance of cellular redox and metabolic homeostasis, as well as the regulation of inflammation and cellular detoxication pathways. The contribution of the NRF2 pathway to organismal homeostasis is seen in many studies using cell lines and animal models, raising intense attention towards targeting its clinical promise. Over the last three decades, an expanding number of clinical studies have examined NRF2 inducers targeting an ever-widening range of diseases. Full understanding of the pharmacokinetic and pharmacodynamic properties of drug candidates rely partly on the identification, validation, and use of biomarkers to optimize clinical applications. This review focuses on results from clinical trials with four agents known to target NRF2 signaling in preclinical studies (dimethyl fumarate, bardoxolone methyl, oltipraz, and sulforaphane), and evaluates the successes and limitations of biomarkers focused on expression of NRF2 target genes and others, inflammation and oxidative stress biomarkers, carcinogen metabolism and adduct biomarkers in unavoidably exposed populations, and targeted and untargeted metabolomics. While no biomarkers excel at defining pharmacodynamic actions in this setting, it is clear that these four lead clinical compounds do touch the NRF2 pathway in humans. |
| first_indexed | 2024-03-10T17:47:11Z |
| format | Article |
| id | doaj.art-b925e72cade746ef8b6808f27e57d504 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T17:47:11Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-b925e72cade746ef8b6808f27e57d5042023-11-20T09:29:08ZengMDPI AGAntioxidants2076-39212020-08-019871610.3390/antiox9080716Current Landscape of NRF2 Biomarkers in Clinical TrialsYoko Yagishita0Tonibelle N. Gatbonton-Schwager1Melissa L. McCallum2Thomas W. Kensler3Fred Hutchinson Cancer Research Center, Translational Research Program, Public Health Sciences Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Translational Research Program, Public Health Sciences Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Translational Research Program, Public Health Sciences Division, Seattle, WA 98109, USAFred Hutchinson Cancer Research Center, Translational Research Program, Public Health Sciences Division, Seattle, WA 98109, USAThe transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by <i>NFE2L2</i>) plays a critical role in the maintenance of cellular redox and metabolic homeostasis, as well as the regulation of inflammation and cellular detoxication pathways. The contribution of the NRF2 pathway to organismal homeostasis is seen in many studies using cell lines and animal models, raising intense attention towards targeting its clinical promise. Over the last three decades, an expanding number of clinical studies have examined NRF2 inducers targeting an ever-widening range of diseases. Full understanding of the pharmacokinetic and pharmacodynamic properties of drug candidates rely partly on the identification, validation, and use of biomarkers to optimize clinical applications. This review focuses on results from clinical trials with four agents known to target NRF2 signaling in preclinical studies (dimethyl fumarate, bardoxolone methyl, oltipraz, and sulforaphane), and evaluates the successes and limitations of biomarkers focused on expression of NRF2 target genes and others, inflammation and oxidative stress biomarkers, carcinogen metabolism and adduct biomarkers in unavoidably exposed populations, and targeted and untargeted metabolomics. While no biomarkers excel at defining pharmacodynamic actions in this setting, it is clear that these four lead clinical compounds do touch the NRF2 pathway in humans.https://www.mdpi.com/2076-3921/9/8/716biomarkersNRF2 (nuclear factor erythroid 2 related factor 2)sulforaphaneoltiprazbardoxolone methyldimethyl fumarate |
| spellingShingle | Yoko Yagishita Tonibelle N. Gatbonton-Schwager Melissa L. McCallum Thomas W. Kensler Current Landscape of NRF2 Biomarkers in Clinical Trials Antioxidants biomarkers NRF2 (nuclear factor erythroid 2 related factor 2) sulforaphane oltipraz bardoxolone methyl dimethyl fumarate |
| title | Current Landscape of NRF2 Biomarkers in Clinical Trials |
| title_full | Current Landscape of NRF2 Biomarkers in Clinical Trials |
| title_fullStr | Current Landscape of NRF2 Biomarkers in Clinical Trials |
| title_full_unstemmed | Current Landscape of NRF2 Biomarkers in Clinical Trials |
| title_short | Current Landscape of NRF2 Biomarkers in Clinical Trials |
| title_sort | current landscape of nrf2 biomarkers in clinical trials |
| topic | biomarkers NRF2 (nuclear factor erythroid 2 related factor 2) sulforaphane oltipraz bardoxolone methyl dimethyl fumarate |
| url | https://www.mdpi.com/2076-3921/9/8/716 |
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