Cancer Medicine (Sep 2023)

The tryptophan–kynurenine pathway in immunomodulation and cancer metastasis

  • Charlise Basson,
  • June Cheptoo Serem,
  • Yvette Nkondo Hlophe,
  • Priyesh Bipath

DOI
https://doi.org/10.1002/cam4.6484
Journal volume & issue
Vol. 12, no. 18
pp. 18691 – 18701

Abstract

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Abstract Introduction The activation of the kynurenine pathway in cancer progression and metastasis through immunomodulatory pathways has drawn attention to the potential for kynurenine pathway inhibition. The activation of the kynurenine pathway, which results in the production of kynurenine metabolites through the degradation of tryptophan, promotes the development of intrinsically malignant properties in cancer cells while facilitating tumour immune escape. In addition, kynurenine metabolites act as biologically active substances to promote cancer development and metastasis. Methods A literature review was conducted to investigate the role of the tryptophan‐kynurenine pathway in immunomodulation and cancer metastasis. Results Evidence suggests that several enzymes and metabolites implicated in the kynurenine pathway are overexpressed in various cancers. As such, the tryptophan pathway represents a promising target for cancer treatment. However, downstream signalling pathways, including aryl hydrocarbon receptor activation, have previously induced diverse biological effects in various malignancies, which resulted in either the promotion or the inhibition of metastasis. Conclusion As a result, a thorough investigation of the kynurenine pathway and its regulatory mechanisms is necessary in order to properly comprehend the effects of kynurenine pathway activation involved in cancer development and metastasis.

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