ArticleCancers2023
Hedgehog-GLI and Notch Pathways Sustain Chemoresistance and Invasiveness in Colorectal Cancer and Their Inhibition Restores Chemotherapy Efficacy.
Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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Who cites it
16 citing papers in PubMed.
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Integrating multi-omics data for next-generation cancer research and precision medicine.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Hyperglycaemia-Induced Metabolic Stress Promotes EMT-Driven Therapeutic Resistance in Cancer: Evidence of a Deleterious Feed-Forward Cycle.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Tumour Jagged1 expression as a prognostic marker of bevacizumab response and modulation of 5-fluorouracil efficacy through γ-secretase inhibition in colorectal cancer.Gastroenterology report · 2026Article
- Evolution or Revolution in Colorectal Cancer Treatment: Present and Future of New Therapeutic Options. A Narrative Review.Oncology research · 2026Review
- Regulatory Signaling Pathways in Ovarian Cancer Stem Cells: Their Role in Tumor Progression and Therapeutic Strategies.Iranian biomedical journal · 2025Review
- Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway.Scientific reports · 2025Article
- Molecular characteristics and cancer immunity of LRP1B and its relationship with the Hedgehog signaling pathway in colorectal cancer.Frontiers in immunology · 2025Article
- Epithelial-mesenchymal plasticity in cancer: signaling pathways and therapeutic targets.MedComm · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- The Impact of Cancer Stem Cells in Colorectal Cancer.International journal of molecular sciences · 2024Review
- Arsenic trioxide: applications, mechanisms of action, toxicity and rescue strategies to date.Archives of pharmacal research · 2024Review
- Gastrointestinal tract organoids as novel tools in drug discovery.Frontiers in pharmacology · 2024Review
- Prognostic potential of whole exome sequencing in the clinical management of metachronous colorectal cancer liver metastases.Cancer cell international · 2023Article
- Tumor Microenvironment Remodeling in Gastrointestinal Cancer: Role of miRNAs as Biomarkers of Tumor Invasion.Biomedicines · 2023Review
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related mortality and chemoresistance is a major medical issue. The epithelial-to-mesenchymal transition (EMT) is the primary step in the emergence of the invasive phenotype and the Hedgehog-GLI (HH-GLI) and NOTCH signaling pathways are associated with poor prognosis and EMT in CRC. CRC cell lines harboring KRAS or BRAF mutations, grown as monolayers and organoids, were treated with the chemotherapeutic agent 5-Fluorouracil (5-FU) alone or combined with HH-GLI and NOTCH pathway inhibitors GANT61 and DAPT, or arsenic trioxide (ATO) to inhibit both pathways. Treatment with 5-FU led to the activation of HH-GLI and NOTCH pathways in both models. In KRAS mutant CRC, HH-GLI and NOTCH signaling activation co-operate to enhance chemoresistance and cell motility, while in BRAF mutant CRC, the HH-GLI pathway drives the chemoresistant and motile phenotype. We then showed that 5-FU promotes the mesenchymal and thus invasive phenotype in KRAS and BRAF mutant organoids and that chemosensitivity could be restored by targeting the HH-GLI pathway in BRAF mutant CRC or both HH-GLI and NOTCH pathways in KRAS mutant CRC. We suggest that in KRAS-driven CRC, the FDA-approved ATO acts as a chemotherapeutic sensitizer, whereas GANT61 is a promising chemotherapeutic sensitizer in BRAF-driven CRC.
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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.