ArticleCancer discovery2022
Synthetic Essentiality of Tryptophan 2,3-Dioxygenase 2 in APC-Mutated Colorectal Cancer.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 49 citations in OpenAlex.
- Integrated spatial and single-cell transcriptomics uncover IFI6⁺ regulatory T-cells and SPP1⁺ macrophages immunosuppressive niches in colorectal cancer.British journal of cancer · 2026Article
- Tryptophan metabolism in colorectal cancer: From mechanistic insights to novel therapeutic strategies.Clinical and translational medicine · 2026Review
- Tryptophan metabolism in tumor microenvironment and therapeutic implications.Journal of advanced research · 2026Review
- Synthetic lethality in cancer: mechanism exploration and therapeutic applications.Cell communication and signaling : CCS · 2026Review
- FGFR1 Promotes Malignant Progression in Lung Squamous Cell Carcinoma Through Activation of Wnt/β-Catenin Signaling.Cancer medicine · 2026Article
- Targeting metabolic-epigenetic-immune axis in cancer: molecular mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Elucidate senescence-related gene signature and immune infiltration landscape in abdominal aortic aneurysm.PloS one · 2026Article
- Reimagining AHR in Cancer: From Environmental Sensor to Novel Immunomodulatory Therapeutic Target.International journal of biological sciences · 2026Review
- Tryptophan metabolism in tumor immune escape: mechanisms, cellular crosstalk, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Identification and characterization of tryptophan metabolism-related genes in carotid artery plaques.PloS one · 2026Article
- Context-dependent functions of the aryl hydrocarbon receptor in gastrointestinal cancers: from microenvironmental regulation to precision targeted therapy.Frontiers in cell and developmental biology · 2026Review
- Amino acid metabolic regulatory network in tumor immune escape: mechanistic exploration and intervention directions.Frontiers in immunology · 2026Review
- AR to GR switch modulates differential TDO2-Kyn-AhR signalling to promote the survival and recurrence of treatment-induced dormant cells in prostate cancer.Cell discovery · 2025Article
- Identification and evaluation of metabolic mRNAs and key miRNAs in colorectal cancer liver metastasis.Cancer cell international · 2025Article
- Cytidine diphosphate diacylglycerol synthase 2 is a synthetic lethal target in mesenchymal-like cancers.Nature genetics · 2025Article
- Synthetic essentiality of TRAIL/TNFSF10 in VHL-deficient renal cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- CCL20/CXCL5 Drives Crosstalk Between Anaplastic Thyroid Cancer Stem Cells and Tumor-Associated Macrophages to Promote Tumor Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Review
- Targeting the Kynurenine Pathway: A Novel Approach in Tumor Therapy.Expert reviews in molecular medicine · 2025Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Inactivation of adenomatous polyposis coli (APC) is common across many cancer types and serves as a critical initiating event in most sporadic colorectal cancers. APC deficiency activates WNT signaling, which remains an elusive target for cancer therapy, prompting us to apply the synthetic essentiality framework to identify druggable vulnerabilities for APC-deficient cancers. Tryptophan 2,3-dioxygenase 2 (TDO2) was identified as a synthetic essential effector of APC-deficient colorectal cancer. Mechanistically, APC deficiency results in the TCF4/β-catenin-mediated upregulation of TDO2 gene transcription. TDO2 in turn activates the Kyn-AhR pathway, which increases glycolysis to drive anabolic cancer cell growth and CXCL5 secretion to recruit macrophages into the tumor microenvironment. Therapeutically, APC-deficient colorectal cancer models were susceptible to TDO2 depletion or pharmacologic inhibition, which impaired cancer cell proliferation and enhanced antitumor immune profiles. Thus, APC deficiency activates a TCF4-TDO2-AhR-CXCL5 circuit that affects multiple cancer hallmarks via autonomous and nonautonomous mechanisms and illuminates a genotype-specific vulnerability in colorectal cancer. SIGNIFICANCE: This study identifies critical effectors in the maintenance of APC-deficient colorectal cancer and demonstrates the relationship between APC/WNT pathway and kynurenine pathway signaling. It further determines the tumor-associated macrophage biology in APC-deficient colorectal cancer, informing genotype-specific therapeutic targets and the use of TDO2 inhibitors. This article is highlighted in the In This Issue feature, p. 1599.
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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.