The essential amino acid tryptophan and the enzymes that cause its degradation influence the regulation of immune, neuronal and intestinal systems. A recent Nature Drug Discovery paper reviewed the potential of tryptophan metabolites as therapeutic targets in a range of diseases, including cancer.
Studies have shown that imbalances in tryptophan metabolism can affect tumor progression. However, there is still a clear lack of understanding of their downstream effector mechanisms. This is exemplified by pathway inhibitor drugs such as IDO1 inhibitors, which showed promise in early-stage trials but later failed in clinical trials. The review highlights the aforementioned importance of comprehensive preclinical target validation when characterizing complex cellular pathways, allowing drug developers to focus resources on programs with a high probability of success.
Read the Nature Drug Discovery paper here.