ArticleMolecular therapy. Methods & clinical development2016
Fbxw7-associated drug resistance is reversed by induction of terminal differentiation in murine intestinal organoid culture.
Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- FBXW7 Gene Mutation and Expression in Colorectal Cancer (CRC): A Systematic Review from Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2025Pooled it
- F-box protein 28 serves as a prognostic and predictive biomarker for gastric cancer.Translational cancer research · 2026Article
- Early mutational events and clonal dynamics in normal crypts: implications for colorectal tumorigenesis.Human genomics · 2025Review
- Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC7.Molecular oncology · 2024Article
- FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies.Frontiers in pharmacology · 2023Review
- Activation of the integrated stress response is a vulnerability for multidrug-resistant FBXW7-deficient cells.EMBO molecular medicine · 2022Article
- Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids.Oncogenesis · 2022Article
- The Potential Role of Genomic Signature in Stage II Relapsed Colorectal Cancer (CRC) Patients: A Mono-Institutional Study.Cancer management and research · 2022Article
- Application Progress of Organoids in Colorectal Cancer.Frontiers in cell and developmental biology · 2022Review
- Role of multidrug resistance-associated proteins in cancer therapeutics: past, present, and future perspectives.Environmental science and pollution research international · 2021Review
- CaCancer science · 2021Article
- Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2.EMBO reports · 2021Article
- Repurposing Antibacterial AM404 as a Potential Anticancer Drug for Targeting Colorectal Cancer Stem-Like Cells.Cancers · 2019Article
- Article
- An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance.Oncogenesis · 2019Article
- FLYWCH1, a Novel Suppressor of Nuclear β-Catenin, Regulates Migration and Morphology in Colorectal Cancer.Molecular cancer research : MCR · 2018Article
- F-box proteins involved in cancer-associated drug resistance.Oncology letters · 2018Review
- Polo-like kinase 2 promotes chemoresistance and predicts limited survival benefit from adjuvant chemotherapy in colorectal cancer.International journal of oncology · 2018Article
- Morphological alterations of cultured human colorectal matched tumour and healthy organoids.Oncotarget · 2018Article
- The nucleocytoplasmic translocation and up-regulation of ING5 protein in breast cancer: a potential target for gene therapy.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is one of the top three cancer-related causes of death worldwide. FBXW7 is a known tumor-suppressor gene, commonly mutated in CRC and in a variety of other epithelial tumors. Low expression of FBXW7 is also associated with poor prognosis. Loss of FBXW7 sensitizes cancer cells to certain drugs, while making them more resistant to other types of chemotherapies. However, is not fully understood how epithelial cells within normal gut and primary tumors respond to potential cancer therapeutics. We have studied genetically engineered mice in which the fbxw7 gene is conditionally knocked-out in the intestine (fbxw7(∆G)). To further investigate the mechanism of Fbxw7-action, we grew intestinal crypts from floxed-fbxw7 (fbxw7(fl/fl)) and fbxw7(ΔG) mice, in a Matrigel-based organoid (mini-gut) culture. The fbxw7(ΔG) organoids exhibited rapid budding events in the crypt region. Furthermore, to test organoids for drug response, we exposed day 3 intestinal organoids from fbxw7(fl/fl) and fbxw7(∆G) mice, to various concentrations of 5-fluorouracil (5-FU) for 72 hours. 5-FU triggers phenotypic differences in organoids including changing shape, survival, resistance, and death. 5-FU however, rescues the drug-resistance phenotype of fbxw7(ΔG) through the induction of terminal differentiation. Our results support the hypothesis that a differentiating therapy successfully targets FBXW7-mutated CRC cells.
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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.