Journal article
Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond.
- Platten M DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), INF 280, Heidelberg, Germany. m.platten@Dkfz-Heidelberg.de.
- Nollen EAA University of Groningen, European Research Institute for the Biology of Ageing, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen, Netherlands.
- Röhrig UF Molecular Modelling Group, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland.
- Fallarino F Department of Experimental Medicine, University of Perugia, Perugia, Italy.
- Opitz CA DKTK Brain Cancer Metabolism Group, German Cancer Research Center (DKFZ), INF 280, Heidelberg, Germany.
- 2019-02-15
Published in:
- Nature reviews. Drug discovery. - 2019
Animals
Antineoplastic Agents
Clinical Trials as Topic
Humans
Metabolic Networks and Pathways
Neoplasms
Neurodegenerative Diseases
Tryptophan
English
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.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1038/s41573-019-0016-5
- PMID 30760888
- Persistent URL
- https://sonar.ch/global/documents/75630
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