ArticleNature cancer2024
Recapitulating the adenoma-carcinoma sequence by selection of four spontaneous oncogenic mutations in mismatch-repair-deficient human colon organoids.
Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Recent Developments and Applicability of In Vitro Gut Microbiota Models in Biomedical Research and Digestive Diseases-A Systematic Review.Medicina (Kaunas, Lithuania) · 2026Pooled it
- Trial
- Colorectal Cancer: Epidemiology, Risk Factors, Signaling Pathways, Clinical Features, Screening, Diagnosis, and Management.MedComm · 2026Review
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
- Mechanism-Driven Diagnostic Development: A Specimen-Aware Framework Illustrated by Colorectal Cancer and Solid Tumours.Cancers · 2026Review
- Whole Tumor Heterogeneity Topography (WTHT)-A New Approach for Assessment of Intratumor Mutational Heterogeneity in Colorectal Adenomas.International journal of molecular sciences · 2026Article
- Gastric Cancer Organoids: Mechanistic Insights, Drug Discovery, and Translational Advances in Precision Medicine.Journal of gastric cancer · 2026Review
- Organoid technology in cancer research.Molecular biomedicine · 2026Review
- Deconstructing cancer in 3D: models, mechanisms, and personalized solutions.Molecular cancer · 2026Review
- Imperatorin: A Furanocoumarin with Potential in Combating Cancer Development and Progression-A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Modeling hepatic fibrosis in TP53 knockout iPSC-derived human liver organoids.Molecular oncology · 2026Article
- The application of experimental models for the drug discovery for digestive tumors.Molecular cancer · 2026Review
- Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026Review
- Computer-aided polyp detection and characterisation systems to support colonoscopy: a systematic review with results stratified by each individual artificial intelligence system.BMJ digital health & AI · 2026Article
- Article
- Targeting TRIM15-mediated Axin1 depolymerization suppresses Wnt signaling and inhibits colorectal cancer growth.Cell death & disease · 2025Article
- Genetic, Epidemiological, Clinical, and Therapeutic Trajectories in Colon and Rectal Cancers.Cancers · 2025Review
- Integration of single-cell and bulk RNA sequencing data to identify liquid-liquid phase separation-related prognostic biomarkers in hepatocellular carcinoma.Scientific reports · 2025Article
- Therapeutic targeting of mismatch repair-deficient cancers.Nature reviews. Clinical oncology · 2025Review
- Immune organoid for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
Carcinogenesis results from the sequential acquisition of oncogenic mutations that convert normal cells into invasive, metastasizing cancer cells. Colorectal cancer exemplifies this process through its well-described adenoma-carcinoma sequence, modeled previously using clustered regularly interspaced short palindromic repeats (CRISPR) to induce four consecutive mutations in wild-type human gut organoids. Here, we demonstrate that long-term culture of mismatch-repair-deficient organoids allows the selection of spontaneous oncogenic mutations through the sequential withdrawal of Wnt agonists, epidermal growth factor (EGF) agonists and the bone morphogenetic protein (BMP) antagonist Noggin, while TP53 mutations were selected through the addition of Nutlin-3. Thus, organoids sequentially acquired mutations in AXIN1 and AXIN2 (Wnt pathway), TP53, ACVR2A and BMPR2 (BMP pathway) and NRAS (EGF pathway), gaining complete independence from stem cell niche factors. Quadruple-pathway (Wnt, EGF receptor, p53 and BMP) mutant organoids formed solid tumors upon xenotransplantation. This demonstrates that carcinogenesis can be recapitulated in a DNA repair-mutant background through in vitro selection that targets four consecutive cancer pathways.
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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.