Cited by 1,586Tryptophan and brain disordersAmino Acid Enzymes and MetabolismCancer Immunotherapy and Biomarkers

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Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond

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Platten, Michael, Nollen, Ellen A. A., Röhrig, Ute F., Fallarino, Francesca, Opitz, Christiane A.·2019·Nature Reviews Drug Discovery

DOI 10.1038/s41573-019-0016-5

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Abstract

L-Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is involved in the regulation of immunity, neuronal function and intestinal homeostasis. Imbalances in Trp metabolism in disorders ranging from cancer to neurodegenerative disease have stimulated interest in therapeutically targeting the KP, particularly the main rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan-2,3-dioxygenase (TDO) as well as kynurenine monooxygenase (KMO). However, although small-molecule IDO1 inhibitors showed promise in early-stage cancer immunotherapy clinical trials, a phase III trial was negative. This Review summarizes the physiological and pathophysiological roles of Trp metabolism, highlighting the vast opportunities and challenges for drug development in multiple diseases.

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UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 46,047
Tissue-based map of the human proteome
Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, Å., Kampf, C., Sjöstedt, E., Asplund, A., et al. (2015) · Science · doi:10.1126/science.1260419 · Cited by 15,286
Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22
Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D’Angelo, C., Massi-Benedetti, C., Fallarino, F., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.003 · Cited by 2,614
Self-citation
Prevention of Allogeneic Fetal Rejection by Tryptophan Catabolism
Munn, D. H., Zhou, M., Attwood, J. T., Bondarev, I. E., Conway, S. J., Marshall, B., Brown, C. C., & Mellor, A. L. (1998) · Science · doi:10.1126/science.281.5380.1191 · Cited by 2,589
Ido expression by dendritic cells: tolerance and tryptophan catabolism
Mellor, A. L., & Munn, D. H. (2004) · Nature Reviews Immunology · doi:10.1038/nri1457 · Cited by 2,341
Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase
Uyttenhove, C., Pilotte, L., Théate, I., Stroobant, V., Colau, D., Parmentier, N., Boon, T., & Van den Eynde, B. J. (2003) · Nature Medicine · doi:10.1038/nm934 · Cited by 2,305
An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor
Opitz, C. A., Litzenburger, U. M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., et al. (2011) · Nature · doi:10.1038/nature10491 · Cited by 1,898
Self-citation
Immunity to fungal infections
Romani, L. (2011) · Nature Reviews Immunology · doi:10.1038/nri2939 · Cited by 1,793
An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells
Mezrich, J. D., Fechner, J. H., Zhang, X., Johnson, B. P., Burlingham, W. J., & Bradfield, C. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903670 · Cited by 1,674
Inhibition of T Cell Proliferation by Macrophage Tryptophan Catabolism
Munn, D. H., Shafizadeh, E., Attwood, J. T., Bondarev, I. E., Pashine, A., & Mellor, A. L. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.9.1363 · Cited by 1,640

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Shi, W., Shen, L., Zou, W., Wang, J., Yang, J., Wang, Y., Liu, B., Xie, L., Zhu, J. Y., & Zhang, Z. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.562463 · Cited by 69
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Liang, H., Li, T., Fang, X., Xing, Z., Zhang, S., Shi, L., Li, W., Guo, L., Kuang, C., Liu, H., et al. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.09.012 · Cited by 67
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Li, B., Zu, M., Jiang, A., Cao, Y., Wu, J., Shahbazi, M.-A., Shi, X., Reis, R. L., Kundu, S. C., & Xiao, B. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122530 · Cited by 67
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Huang, X., Zhang, F., Wang, X., & Liu, K. (2022) · Cancers · doi:10.3390/cancers14112756 · Cited by 69
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Niu, B., Pan, T., Xiao, Y., Wang, H., Zhu, J., Tian, F., Lu, W., & Chen, W. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2299744 · Cited by 66
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Self-citation

Authors: Platten, M., Nollen, E. A. A., Röhrig, U. F., Fallarino, F., & Opitz, C. A.
Affiliations: German Cancer Research Center (DE)
University Medical Center Groningen (NL)
SIB Swiss Institute of Bioinformatics (CH)
University of Perugia (IT)
Corresponding author: Platten, Michael
ORCID: Platten, Michael
Nollen, Ellen A. A.
Röhrig, Ute F.
Fallarino, Francesca
Opitz, Christiane A.
Venue: Nature Reviews Drug Discovery
Publisher: Springer Science and Business Media LLC
Published: 2019-02-13
Volume: 18
Issue: 5
Pages: 379-401
ISSN: 1474-1776 (ISSN-L)
1474-1784
DOI: 10.1038/s41573-019-0016-5
OpenAlex: W2912181843
Cited by: 1,586
References: 292
Citations by year: 2026: 245 · 2025: 278 · 2024: 284 · 2023: 241 · 2022: 220 · 2021: 176 · 2020: 119 · 2019: 23
FWCI: 8.66
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Drug Discovery (publishedVersion)
PubMed (publishedVersion)
University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: tryptophan metabolism, kynurenine pathway, IDO1 inhibitors, indoleamine 2,3-dioxygenase, IDO2, tryptophan 2,3-dioxygenase, kynurenine monooxygenase, cancer immunotherapy, neurodegeneration, autoimmune disease, infectious diseases, central nervous system disorders, drug development
MeSH terms: Animals, Antineoplastic Agents, Clinical Trials as Topic, Humans, Neoplasms, Tryptophan, Neurodegenerative Diseases, Metabolic Networks and Pathways

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Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond

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