New insights into tryptophan metabolism in cancer
Zhe Qi Liu1, M Teresa Ciudad1, Tracy L McGaha1
1Tumor Immunotherapy Program Princess Margaret Cancer Centre, Toronto, ON, M5G 2M9, Canada; Department of Immunology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Abstract:
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.
Insights
Tryptophan metabolism is crucial for cancer growth and immune suppression. Despite early trial failures, new insights into its complex role necessitate reconsidering tryptophan pathways for cancer therapy.
Area of Science:
- Biochemistry
- Immunology
- Oncology
Background:
- Tryptophan (Trp) is essential for biological processes.
- Altered Trp metabolism supports cancer survival and growth.
- Trp metabolism links to immune suppression, prompting clinical trials.
Purpose of the Study:
- To review recent advancements in understanding Trp metabolism.
- To address contradictions in current Trp metabolism research.
- To explore Trp pathway adaptations impacting cancer therapy.
Main Methods:
- Literature review of Trp metabolism studies.
- Analysis of Trp circuits in tumor-immune-microbiota interactions.
- Discussion of therapeutic manipulations and adaptations.
Main Results:
- Early clinical trials targeting Trp metabolism in melanoma failed.
- Recent findings reveal complex Trp circuits and interactions.
- Adaptations in Trp pathways can influence treatment outcomes.
Conclusions:
- Reconsideration of Trp metabolism is vital due to new insights.
- Understanding Trp pathway interplay is key for effective cancer therapies.
- Further research into Trp metabolism adaptations is needed.
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