Targeting regulation of tryptophan metabolism for colorectal cancer therapy: a systematic review

Abstract

Colorectal cancer (CRC) is one of the most malignant cancers resulting from abnormal metabolism alterations. As one of the essential amino acids, tryptophan has a variety of physiological functions, closely related to regulation of immune system, central nervous system, gastrointestinal nervous system and intestinal microflora. Colorectal cancer, a type of high-grade malignancy disease, stems from a variety of factors and often accompanies inflammatory reactions, dysbacteriosis, and metabolic disorders. Colorectal cancer accompanies inflammation and imbalance of intestinal microbiota and affects tryptophan metabolism. It is known that metabolites, rate-limiting enzymes, and ARH in tryptophan metabolism are associated with the development of CRC. Specifically, IDO1 may be a potential therapeutic target in colorectal cancer treatment. Furthermore, the reduction of tryptophan amount is proportional to the poor quality of life for colorectal cancer patients. This paper aims to discuss the role of tryptophan metabolism in a normal organism and investigate the relationship between this amino acid and colorectal cancer. This study is expected to provide theoretical support for research related to targeted therapy for colorectal cancer. Furthermore, strategies that modify tryptophan metabolism, effectively inhibiting tumor progression, may be more effective for CRC treatment.

Fig. 1. The two main pathways of tryptophan metabolism in vivo. IDO: indoleamine-2,3-dioxygenase; TDO: toluene dioxygenase; TPH: tryptophan hydroxylase MAO: monoamine oxidase; SNAT: N-acetyltransferase.

Fig. 2. A schematic diagram of the physiological function of tryptophan metabolism.

Fig. 3. Schematic representation of tryptophan metabolism in the process of CRC development. TRP: tryptophan; DC: dendritic cells; IDO: indoleamine-2,3-dioxygenase, IDO mainly is IDO1 in this paper; ARH: aromatic hydrocarbon receptor; GCN2: stress response kinase GCN2; APC: antigen-presenting cell.