New insights into tryptophan metabolism in cancer.

Tryptophan (Trp) is an essential amino acid and key intermediate in a range of biological processes. Early studies identified altered Trp utilization in cancer cells favoring cancer survival and growth. Seminal findings linking Trp metabolism and suppression of immunity led to an explosion of interest ultimately culminating in clinical trials targeting these pathways in melanoma. The failure of these trials led to a clinical retreat in this approach; however, recent insights into the complex interplay of the various Trp circuits and between tumor cells, immune cells, and the microbiota have shown that reconsideration of Trp metabolism is needed. Here, we discuss recent developments in our understanding of Trp metabolism and apparent contradictions in the field. We also discuss adaptations that occur when Trp pathways are manipulated, which may impact therapy responses.