Exploring the importance of kynurenine pathway (KP) approaches in colorectal cancer (CRC)

Abstract

One of the main causes of cancer-related fatalities is colorectal cancer (CRC). The majority of patients frequently receive a late diagnosis of colorectal cancer (CRC) due to the absence of accurate prognostic and predictive biomarkers. Furthermore, greater metastasis and shorter survival rates were seen in colorectal cancer (CRC) patients. Recent advances in cancer treatment have been made possible by therapeutic immune system potentiation. The immune system and the kynurenine pathway (KP) are closely related. As a result of kynurenine's promotion of T Reg (regulatory) differentiation, more anti-inflammatory cytokines are produced and the cytotoxic activity of T cells is suppressed. In malignancies, the overactivation of the kynurenine pathway (KP) creates a micro environment where mutant cells can survive and invade neighboring tissues.The poor prognosis of several cancers, including gastrointestinal cancers, gynecological cancers, hematologic malignancies, breast cancer, lung cancer, glioma, melanoma, prostate cancer, and pancreatic cancer, is predicted by overactivation of the kynurenine pathway (KP), particularly the overactivation of indoleamine 2,3-dioxygenase (IDO). Additionally, kynurenine promotes cancer cell invasion, metastasis, and chemoresistance. The evolving understanding of the kynurenine pathway (KP) and its use in colorectal cancer (CRC) is covered in this review. An essential amino acid called tryptophan can be processed by several different pathways, with the kynurenine pathway (KP) being one of the more important ones. Kynurenine (KYN) is recognized as an oncometabolite in colon cancer, and colorectal cancer (CRC) that results from its subsequent metabolites. For several physiological activities, indoleamine 2,3-dioxygenase (IDO), a crucial enzyme that catalyzes kynurenine metabolism, is required. We talked about IDO's role in colorectal cancer (CRC) in this review. IDO knockdown decreased the expression of cancer stem cell markers as well as the ability of colorectal cancer (CRC) cells to migrate and invade. The application of an inhibitor to restrict the enzymatic activity of IDO also prevented the formation of spheres and hindered cell motility in colorectal cancer (CRC) cells. These findings demonstrate the clinical significance of IDO in the growth and tumorigenicity of colorectal cancer (CRC) tumors.