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Review
. 2019 May;18(5):379-401.
doi: 10.1038/s41573-019-0016-5.

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

Michael Platten  1   2 , Ellen A A Nollen  3 , Ute F Röhrig  4 , Francesca Fallarino  5 , Christiane A Opitz  6   7
Affiliations
Review

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

Michael Platten et al. Nat Rev Drug Discov. 2019 May.

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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