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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“The single nucleotide polymorphism of the KMO gene is related to SCZ, further supporting the notion that the decrease in the 3-HK branch in the KP pathway may cause L-KYN to convert to KYNA, which is one of the causes of SCZ [19].”
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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
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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