ArticleCell reports. Medicine2024
An RNA damage response network mediates the lethality of 5-FU in colorectal cancer.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Heterozygous loss-of-function alleles associate the conserved 3'-5' exoribonuclease EXOSC10 with hypersensitivity to the anticancer drug 5-fluorouracil.Molecular oncology · 2026Article
- Expression of Thymidylate Synthase in Cancer: A Tissue Microarray Study Involving 17,371 Cancers from 136 Tumor Entities.Biomedicines · 2026Article
- Repurposed cAMP-Modulating Agents Enhance 5-Fluorouracil Response Through Membrane-Dependent Mechanisms.Membranes · 2026Review
- (Journal of medicinal chemistry · 2026Article
- 5-Azacytidine incorporation into mRNAs disrupts translation and induces ribosome collisions.bioRxiv : the preprint server for biology · 2026Article
- Metabolism of Epigenetic Ribonucleosides Leads to Nucleolar Stress and Cytotoxicity.ACS chemical biology · 2026Article
- Comparative Proteomic Profiling of Responses to Standard Systemic Treatment Regimens in Pancreatic Cancer.Cells · 2026Article
- CF10 Displays Improved Synergy with Oxaliplatin inCancers · 2026Article
- A Classifier for Patient-Derived Colorectal Tumoroid Drug Sensitivity Using Confocal Imaging and Growth Rate Inhibition Metrics.Cancer research communications · 2026Article
- AquIRE reveals the mechanisms of clinically induced RNA damage and the conservation and dynamics of glycoRNAs.Nucleic acids research · 2026Article
- Metal-ion-coordinated silk fibroin nanogels for enhanced oral chemotherapy of colorectal cancer.Journal of nanobiotechnology · 2026Article
- The mTORC2 component SIN1 post-transcriptionally regulates TYMS levels and modulates P53 activity in response to 5-FU chemotherapy.Cell communication and signaling : CCS · 2026Article
- Nucleophosmin supports WNT-driven hyperproliferation and tumor initiation.Nature genetics · 2026Article
- Calcitriol Modulates Age-dependent Drug Response in Paired Patient-derived Normal and Tumor Colorectal Organoids.International journal of biological sciences · 2026Article
- Transcriptome-wide mapping reveals an RNA-dependent mechanism of platinum cancer drugs.bioRxiv : the preprint server for biology · 2025Article
- Causes and consequences of RNA:protein cross-links - lessons from chemotherapy.Emerging topics in life sciences · 2025Review
- Polyamines sustain epithelial regeneration in aged intestines by modulating protein homeostasis.Nature cell biology · 2025Article
- Combined Treatment of Sodium Butyrate and Bromelain Enhanced Anticancer Effects in Colorectal Cancer Cell Lines: A Promising Therapeutic Approach.International journal of molecular sciences · 2025Article
- Enhanced Apoptosis in Melanoma Cells via Synergistic Action of Luteolin and 5-FU Through Oxidative Stress Modulation.Applied biochemistry and biotechnology · 2025Article
- Targeting ribosomes reprograms the tumour microenvironment and augments cancer immunotherapy.British journal of cancer · 2025Article
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20 authors.
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Abstract
5-fluorouracil (5-FU), a major anti-cancer therapeutic, is believed to function primarily by inhibiting thymidylate synthase, depleting deoxythymidine triphosphate (dTTP), and causing DNA damage. Here, we show that clinical combinations of 5-FU with oxaliplatin or irinotecan show no synergy in human colorectal cancer (CRC) trials and sub-additive killing in CRC cell lines. Using selective 5-FU metabolites, phospho- and ubiquitin proteomics, and primary human CRC organoids, we demonstrate that 5-FU-mediated CRC cell killing primarily involves an RNA damage response during ribosome biogenesis, causing lysosomal degradation of damaged rRNAs and proteasomal degradation of ubiquitinated ribosomal proteins. Tumor types clinically responsive to 5-FU treatment show upregulated rRNA biogenesis while 5-FU clinically non-responsive tumor types do not, instead showing greater sensitivity to 5-FU's DNA damage effects. Finally, we show that treatments upregulating ribosome biogenesis, including KDM2A inhibition, promote RNA-dependent cell killing by 5-FU, demonstrating the potential for combinatorial targeting of this ribosomal RNA damage response for improved cancer therapy.
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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.