ArticlePloS one2011
Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Targeting Genome Maintenance Defects of Cancers Using Chain-Terminating Nucleoside Analogs.Cancer science · 2026Review
- REV3 promotes cellular tolerance to 5-fluorodeoxyuridine by activating translesion DNA synthesis and intra-S checkpoint.PLoS genetics · 2024Article
- Inhibition of Human Uracil DNA Glycosylase Sensitizes a Large Fraction of Colorectal Cancer Cells to 5-Fluorodeoxyuridine and Raltitrexed but Not Fluorouracil.Molecular pharmacology · 2021Article
- Olaparib-mediated enhancement of 5-fluorouracil cytotoxicity in mismatch repair deficient colorectal cancer cells.BMC cancer · 2021Article
- History of intraperitoneal platinum drug delivery for ovarian cancer and its future applications.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Identification of PARP-1 in cancer stem cells of gastrointestinal cancers: A preliminary study.Journal of biosciences · 2021Article
- Selective depletion of metastatic stem cells as therapy for human colorectal cancer.EMBO molecular medicine · 2018Article
- MACROD2 expression predicts response to 5-FU-based chemotherapy in stage III colon cancer.Oncotarget · 2018Article
- The Inhibitory Effects of HYDAMTIQ, a Novel PARP Inhibitor, on Growth in Human Tumor Cell Lines With Defective DNA Damage Response Pathways.Oncology research · 2017Article
- Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy.Oncotarget · 2017Article
- Glycogen Synthase Kinase 3 (GSK-3)-mediated Phosphorylation of Uracil N-Glycosylase 2 (UNG2) Facilitates the Repair of Floxuridine-induced DNA Lesions and Promotes Cell Survival.The Journal of biological chemistry · 2016Article
- Transcriptome profiling identifies genes and pathways deregulated upon floxuridine treatment in colorectal cancer cells harboring GOF mutant p53.Genomics data · 2016Article
- Genomically Incorporated 5-Fluorouracil that Escapes UNG-Initiated Base Excision Repair Blocks DNA Replication and Activates Homologous Recombination.Molecular pharmacology · 2016Article
- Dietary supplementation with omega-3 fatty acid attenuates 5-fluorouracil induced mucositis in mice.Lipids in health and disease · 2015Article
- Poly (ADP-ribose) polymerase inhibitors: recent advances and future development.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Review
- Standing the test of time: targeting thymidylate biosynthesis in cancer therapy.Nature reviews. Clinical oncology · 2014Review
- Human apurinic/apyrimidinic endonuclease 1.Antioxidants & redox signaling · 2014Review
- The cancer therapeutic potential of Chk1 inhibitors: how mechanistic studies impact on clinical trial design.British journal of clinical pharmacology · 2013Review
- Article
- Identification of DNA repair pathways that affect the survival of ovarian cancer cells treated with a poly(ADP-ribose) polymerase inhibitor in a novel drug combination.Molecular pharmacology · 2012Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The fluoropyrimidines 5-fluorouracil (5-FU) and FdUrd (5-fluorodeoxyuridine; floxuridine) are the backbone of chemotherapy regimens for colon cancer and other tumors. Despite their widespread use, it remains unclear how these agents kill tumor cells. Here, we have analyzed the checkpoint and DNA repair pathways that affect colon tumor responses to 5-FU and FdUrd. These studies demonstrate that both FdUrd and 5-FU activate the ATR and ATM checkpoint signaling pathways, indicating that they cause genotoxic damage. Notably, however, depletion of ATM or ATR does not sensitize colon cancer cells to 5-FU, whereas these checkpoint pathways promote the survival of cells treated with FdUrd, suggesting that FdUrd exerts cytotoxicity by disrupting DNA replication and/or inducing DNA damage, whereas 5-FU does not. We also found that disabling the base excision (BER) repair pathway by depleting XRCC1 or APE1 sensitized colon cancer cells to FdUrd but not 5-FU. Consistent with a role for the BER pathway, we show that small molecule poly(ADP-ribose) polymerase 1/2 (PARP) inhibitors, AZD2281 and ABT-888, remarkably sensitized both mismatch repair (MMR)-proficient and -deficient colon cancer cell lines to FdUrd but not to 5-FU. Taken together, these studies demonstrate that the roles of genotoxin-induced checkpoint signaling and DNA repair differ significantly for these agents and also suggest a novel approach to colon cancer therapy in which FdUrd is combined with a small molecule PARP inhibitor.
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