Participation of DNA repair in the response to 5-fluorouracil.
Article Details
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Wyatt MD, Wilson DM 3rd
Participation of DNA repair in the response to 5-fluorouracil.
Cell Mol Life Sci. 2009 Mar;66(5):788-99. doi: 10.1007/s00018-008-8557-5.
- PubMed ID
- 18979208 [ View in PubMed]
- Abstract
The anti-metabolite 5-fluorouracil (5-FU) is employed clinically to manage solid tumors including colorectal and breast cancer. Intracellular metabolites of 5-FU can exert cytotoxic effects via inhibition of thymidylate synthetase, or through incorporation into RNA and DNA, events that ultimately activate apoptosis. In this review, we cover the current data implicating DNA repair processes in cellular responsiveness to 5-FU treatment. Evidence points to roles for base excision repair (BER) and mismatch repair (MMR). However, mechanistic details remain unexplained, and other pathways have not been exhaustively interrogated. Homologous recombination is of particular interest, because it resolves unrepaired DNA intermediates not properly dealt with by BER or MMR. Furthermore, crosstalk among DNA repair pathways and S-phase checkpoint signaling has not been examined. Ongoing efforts aim to design approaches and reagents that (i) approximate repair capacity and (ii) mediate strategic regulation of DNA repair in order to improve the efficacy of current anticancer treatments.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Capecitabine DNA Nucleotide Humans YesIncorporation into and destabilizationInhibition of synthesisDetails Capecitabine RNA Nucleotide Humans YesIncorporation into and destabilizationDetails Fluorouracil DNA Nucleotide Humans YesIncorporation into and destabilizationDetails Fluorouracil RNA Nucleotide Humans YesIncorporation into and destabilizationDetails - Drug Reactions
Reaction Details
