Kynurenines as a Novel Target for the Treatment of Malignancies

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.

Lichen-Derived Compounds and Extracts as Biologically Active Substances with Anticancer and Neuroprotective Properties

“…However, previous studies proved that combination of IDO1 inhibitors with chemo-or immunotherapy led to an increased response rate when compared to classical therapies. The use of IDO1 inhibitors as add-on therapy can also be effective in inhibiting IDO-induced angiogenesis and thus reducing tumor growth and metastatic potential [49]. Due to the fact that IDO activation plays a pivotal role in the processes of cancer initiation, progression and metastasis, lichen extracts could possibly be used as dietary supplements in chemoprevention of cancer as well.…”

UVB Radiation and Selected Tryptophan-Derived AhR Ligands—Potential Biological Interactions in Melanoma Cells

“…However, it should be noted that tryptophan metabolites may also be involved in the activation of the immune system. KYN is considered to be the most potent immunosuppressant among tryptophan metabolites and it may play a crucial role in cancer immune escape and tumor resistance to immunotherapy [ 51 ]. Additionally, Labadie et al reported that the tryptophan–KYN–AhR pathway may be involved in the immunosuppression of T cell-inflamed tumors, including melanoma [ 52 ].…”

Molecular Targets of Natural Compounds with Anti-Cancer Properties

“…On the other hand, a rapid depletion of tryptophan from the microenvironment can induce stress signals to T cells, promoting CD4 differentiation toward regulatory T cells (Tregs) [147][148][149]. Moreover, in oral cancer cell lines, EGCG displayed the ability to decrease IDO expression by inhibiting INFγ activity [150,151]. Interestingly, green tea polyphenols can also inhibit phosphorylation of STAT1 and its translocation to nucleus.…”