ArticleOncotarget2015
5-Fluorouracil sensitizes colorectal tumor cells towards double stranded DNA breaks by interfering with homologous recombination repair.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- Evaluating KRAS-Associated Responses to Sulfasalazine and 5-Fluorouracil in Colorectal Cancer Using Integrated 2D and PEGDA Microwell-Based 3D Tumor Models.International journal of molecular sciences · 2026Article
- Convergent adaptive architectures linking chemoresistance and radioresistance in chemoradiotherapy: a systems-level perspective.Frontiers in oncology · 2026Review
- BMP antagonist CHRDL2 enhances the cancer stem-cell phenotype and increases chemotherapy resistance in colorectal cancer.Molecular oncology · 2025Article
- Article
- An RNA damage response network mediates the lethality of 5-FU in colorectal cancer.Cell reports. Medicine · 2024Article
- The epigenetic modifier HDAC2 and the checkpoint kinase ATM determine the responses of microsatellite instable colorectal cancer cells to 5-fluorouracil.Cell biology and toxicology · 2023Article
- Mitochondrial metabolism: a predictive biomarker of radiotherapy efficacy and toxicity.Journal of cancer research and clinical oncology · 2023Review
- Hybrid-DIA: intelligent data acquisition integrates targeted and discovery proteomics to analyze phospho-signaling in single spheroids.Nature communications · 2023Article
- Combined Biological and Numerical Modeling Approach for Better Understanding of the Cancer Viability and Apoptosis.Pharmaceutics · 2023Article
- An RNA Damage Response Network Mediates the Lethality of 5-FU in Clinically Relevant Tumor Types.bioRxiv : the preprint server for biology · 2023Article
- Heterogeneity characterization of hepatocellular carcinoma based on the sensitivity to 5-fluorouracil and development of a prognostic regression model.Frontiers in pharmacology · 2023Article
- Computational analysis of 5-fluorouracil anti-tumor activity in colon cancer using a mechanistic pharmacokinetic/pharmacodynamic model.PLoS computational biology · 2022Article
- Fanconi Anemia Pathway in Colorectal Cancer: A Novel Opportunity for Diagnosis, Prognosis and Therapy.Journal of personalized medicine · 2022Review
- Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment.Biology · 2021Review
- B7 homologue 3 as a prognostic biomarker and potential therapeutic target in gastrointestinal tumors.World journal of gastrointestinal oncology · 2021Review
- Review
- Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells.BMC cancer · 2021Article
- Quinacrine-Mediated Inhibition of Nrf2 Reverses Hypoxia-Induced 5-Fluorouracil Resistance in Colorectal Cancer.International journal of molecular sciences · 2019Article
- ATR activated by EB virus facilitates chemotherapy resistance to cisplatin or 5-fluorouracil in human nasopharyngeal carcinoma.Cancer management and research · 2019Article
- The signaling involved in autophagy machinery in keratinocytes and therapeutic approaches for skin diseases.Oncotarget · 2016Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malignant tumors of the rectum are treated by neoadjuvant radiochemotherapy. This involves a combination of 5-fluorouracil (5-FU) and double stranded DNA-break (DSB)-inducing radiotherapy. Here we explored how 5-FU cooperates with DSB-induction to achieve sustainable DNA damage in colorectal cancer (CRC) cells. After DSB induction by neocarzinostatin, phosphorylated histone 2AX (γ-H2AX) rapidly accumulated but then largely vanished within a few hours. In contrast, when CRC cells were pre-treated with 5-FU, gammaH2AX remained for at least 24 hours. GFP-reporter assays revealed that 5-FU decreases the efficiency of homologous recombination (HR) repair. However, 5-FU did not prevent the initial steps of HR repair, such as the accumulation of RPA and Rad51 at nuclear foci. Thus, we propose that 5-FU interferes with the continuation of HR repair, e. g. the synthesis of new DNA strands. Two key mediators of HR, Rad51 and BRCA2, were found upregulated in CRC biopsies as compared to normal mucosa. Inhibition of HR by targeting Rad51 enhanced DNA damage upon DSB-inducing treatment, outlining an alternative way of enhancing therapeutic efficacy. Taken together, our results strongly suggest that interfering with HR represents a key mechanism to enhance the efficacy when treating CRC with DNA-damaging 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.