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

Platten, M., Nollen, E. A. A., Röhrig, U. F., Fallarino, F. & Opitz, C. A., May-2019, In : Nature Reviews Drug Discovery. 18, 8, p. 379-401 23 p.

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

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DOI

  • Michael Platten
  • Ellen A A Nollen
  • Ute F Röhrig
  • Francesca Fallarino
  • Christiane A Opitz

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.

Original languageEnglish
Pages (from-to)379-401
Number of pages23
JournalNature Reviews Drug Discovery
Volume18
Issue number8
Publication statusPublished - May-2019

ID: 79732927