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Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond
Open accessAbstract
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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Metadata
- 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
- Venue
- Nature Reviews Drug Discovery
- Published
- 2019-02-13
- Volume
- 18
- Issue
- 5
- Pages
- 379-401
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- 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
- 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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