Mor Adrian, Tankiewicz-Kwedlo Anna, Pawlak Dariusz
Department of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2c, 15-222 Bialystok, Poland.
Department of Monitored Pharmacotherapy, Medical University of Bialystok, Mickiewicza 2c, 15-222 Bialystok, Poland.
Pharmaceuticals (Basel). 2021 Jun 23;14(7):606. doi: 10.3390/ph14070606.
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.
恶性肿瘤无疑是一个重大的公共卫生问题。其有效治疗仍然是现代医学面临的一大挑战。肿瘤已经发展出多种机制来逃避免疫反应和治疗反应。因此，针对克服这一问题的解决方案的研究存在未满足的临床需求。色氨酸代谢产物在犬尿氨酸途径中的积累会增强肿瘤进展，因为它会抑制免疫系统对癌细胞的反应。它们还参与了抗肿瘤治疗耐药机制的形成。犬尿氨酸是该途径中最有效的免疫抑制代谢产物之一，对恶性肿瘤的发展有重大影响。这一事实促使研究人员评估靶向负责其合成的酶是否可能是治疗各种癌症的有效策略。迄今为止，已经针对这一主题进行了大量临床前和临床研究，特别是关于吲哚胺2,3-双加氧酶活性的抑制，其结果值得关注。这篇综述收集并系统整理了关于犬尿氨酸途径在肿瘤进展中的作用的知识，以及调节其活性在抗癌治疗中的有用性的研究结果。
