Kynurenines as a Novel Target for the Treatment of Malignancies
Adrian Mor1, Anna Tankiewicz-Kwedlo2, Dariusz Pawlak1
1Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2c, 15-222 Bialystok, Poland.
Abstract:
Malignancies are unquestionably a significant public health problem. Their effective treatment is still a big challenge for modern medicine. Tumors have developed a wide range of mechanisms to evade an immune and therapeutic response. As a result, there is an unmet clinical need for research on solutions aimed at overcoming this problem. An accumulation of tryptophan metabolites belonging to the kynurenine pathway can enhance neoplastic progression because it causes the suppression of immune system response against cancer cells. They are also involved in the development of the mechanisms responsible for the resistance to antitumor therapy. Kynurenine belongs to the most potent immunosuppressive metabolites of this pathway and has a significant impact on the development of malignancies. This fact prompted researchers to assess whether targeting the enzymes responsible for its synthesis could be an effective therapeutic strategy for various cancers. To date, numerous studies, both preclinical and clinical, have been conducted on this topic, especially regarding the inhibition of indoleamine 2,3-dioxygenase activity and their results can be considered noteworthy. This review gathers and systematizes the knowledge about the role of the kynurenine pathway in neoplastic progression and the findings regarding the usefulness of modulating its activity in anticancer therapy.
Insights
Targeting the kynurenine pathway, which promotes cancer growth and immune evasion, offers a promising strategy for new anticancer therapies. Inhibiting key enzymes shows noteworthy potential in preclinical and clinical studies.
Area of Science:
- Oncology
- Immunology
- Metabolism
Background:
- Malignancies pose a significant public health challenge, with tumors developing resistance to immune and therapeutic responses.
- The kynurenine pathway (KP) metabolites accumulate, suppressing anti-cancer immune responses and contributing to therapeutic resistance.
- Kynurenine, a potent KP immunosuppressive metabolite, significantly impacts cancer progression.
Purpose of the Study:
- To review the role of the kynurenine pathway in cancer progression.
- To summarize findings on modulating KP activity for anticancer therapy.
- To assess the therapeutic potential of targeting KP enzymes.
Main Methods:
- Systematic review of preclinical and clinical studies.
- Analysis of research on kynurenine pathway metabolites and their impact on cancer.
- Evaluation of studies targeting indoleamine 2,3-dioxygenase (IDO) activity.
Main Results:
- The kynurenine pathway promotes neoplastic progression by suppressing immune responses.
- KP metabolites contribute to resistance against antitumor therapies.
- Inhibition of enzymes like indoleamine 2,3-dioxygenase (IDO) shows promising results in cancer treatment.
Conclusions:
- Modulating the kynurenine pathway is a viable strategy for overcoming cancer immune evasion and therapeutic resistance.
- Targeting KP enzymes represents a promising avenue for novel anticancer therapies.
- Further research and clinical application of KP-targeting agents are warranted.
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