ArticlePloS one2017
Extreme low dose of 5-fluorouracil reverses MDR in cancer by sensitizing cancer associated fibroblasts and down-regulating P-gp.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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
11 citing papers in PubMed.
- Cancer-associated fibroblasts, tumor and radiotherapy: interactions in the tumor micro-environment.Journal of experimental & clinical cancer research : CR · 2024Review
- Cyclodextrin Metal-Organic Frameworks as a Drug Delivery System for Selected Active Pharmaceutical Ingredients.ACS omega · 2024Article
- Review
- Molecular and cellular paradigms of multidrug resistance in cancer.Cancer reports (Hoboken, N.J.) · 2022Review
- Repurposing Alone and in Combination of the Antiviral Saquinavir with 5-Fluorouracil in Prostate and Lung Cancer Cells.International journal of molecular sciences · 2022Article
- Traditional Chinese medicine reverses cancer multidrug resistance and its mechanism.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment.Cancers · 2021Review
- Tumor-Associated Fibroblast-Targeting Nanoparticles for Enhancing Solid Tumor Therapy: Progress and Challenges.Molecular pharmaceutics · 2021Review
- Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer.Signal transduction and targeted therapy · 2021Review
- Searching for Goldilocks: How Evolution and Ecology Can Help Uncover More Effective Patient-Specific Chemotherapies.Cancer research · 2020Review
- Heart failure as interstitial cancer: emergence of a malignant fibroblast phenotype.Nature reviews. Cardiology · 2020Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
We conducted a prospective, meaningful study of extreme low dose of 5-fluorouracil (5FU) as a metronomic agent targeting cancer associated fibroblasts (CAFs) to reverse Multidrug resistance (MDR) by sensitizing cancer associated fibroblasts and down-regulating P-glycoprotein (P-gp). The combination of 5FU and Taxol inhibited resistant KB-8-5 tumor growth by 79% and H460/Tax-R tumor growth by 55%. The inhibition was significant for both tumor types compared with Taxol treatment alone (p<0.001 and p = 0.0067, respectively). Nevertheless, the low-dose 5FU (2.2 mg/kg compared to the therapeutic dose of 50-150 mg/kg) showed negligible tumor inhibitory effect. The tumor growth inhibition study on resistant tumors demonstrated that the continuous administration of low dose 5FU with Taxol significantly inhibited the tumor growth. The treatment overcomes drug resistance in tumors by down-regulating multi-drug resistance transporter protein (P-gp), and more importantly, by eliminating CAFs recruited by resistant tumors. Compared with traditional metronomic chemotherapy, 5FU as metronomic agent targeting CAFs can avoid the disadvantages resulted from the concomitant administration of antiangiogenetic drug. The approach has good translational potential for clinical trials when treating stroma-rich drug resistant tumors.
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