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

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

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

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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Crossref · 10.1038/s41573-019-0016-5

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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
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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