ReviewClinical and translational medicine2026
Tryptophan metabolism in colorectal cancer: From mechanistic insights to novel therapeutic strategies.
Review in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
backgroundTryptophan metabolism drives colorectal cancer (CRC) pathogenesis through three interconnected cascades: the kynurenine pathway, the serotonin pathway, and the gut-microbiota-dominated indole pathway. These pathways exert context-dependent dual activities determined by disease stage, metabolite concentration, cell type and tumor microenvironment. Substrate competition and metabolic flux redistribution occur across the three branches, while extra-intestinal tryptophan metabolites mediate multi-organ crosstalk. Despite substantial preclinical findings, clinical translation is hindered by imperfect predictive biomarkers, therapeutic bypass resistance and insufficient causal evidence for the microbiota-metabolite-host axis. MAIN BODY: This review summarizes biotransformation features and substrate-competing networks of tryptophan metabolism. The kynurenine pathway, responsible for approximately 95% of systemic tryptophan catabolism, exerts stage-dependent dual roles. Its plasma- and feces-derived metabolites and rate-limiting enzyme indoleamine 2,3-dioxygenase 1 show diagnostic and prognostic potential, yet monotherapies targeting this enzyme yield poor outcomes due to interleukin-4-induced gene 1-mediated bypass resistance. The serotonin pathway accounts for only 1%-2% of tryptophan flux; it is predominantly tumor-promoting and protective solely in early-phase colitis-associated tumorigenesis. Selective serotonin reuptake inhibitors hold promise for chemoprevention and immunotherapy sensitization. The microbiota-governed indole pathway generates diverse compounds: indole-3-lactic acid, indole-3-acetic acid and indole-3-propionic acid boost programmed cell death protein 1 (PD-1)-based therapeutic efficacy; indole-3-acrylic acid and 3-methylindole facilitate tumor progression; indole-3-acetaldehyde displays concentration-dependent bidirectional effects. We also discuss natural-product-based and microbiota-targeted interventions, as well as key experimental bottlenecks.
conclusionPreclinical metabolite-guided personalized therapy for CRC requires multi-omics, stable-isotope tracing and organoid-based large-scale prospective cohorts. Standardized patient stratification and clarification of causal metabolic networks are urgently needed.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.