The fluoropyrimidine polymer CF10 synergizes with 5-ethynyl-2'-deoxyuridine by promoting telomere attrition and mitotic catastrophe.

ABSTRACT: Fluoropyrimidine (FP) drugs, including 5-fluorouracil (5FU), are widely used to treat colorectal cancer (CRC) and target de novo thymidine biosynthesis, resulting in DNA damage and cell death. 5-ethynyl-2'-deoxyuridine (EdU) is a thymidine analog that also causes DNA damage. We investigated synergy between FPs and EdU potentially due to increased EdU incorporation into DNA under thymine-less conditions. Using the highest single agent model, strong synergy was observed between a 2nd-generation FP polymer, CF10, and EdU over a wide range of concentrations. In contrast, only additivity was observed for EdU + 5FU. CRC cells treated with synergistic EdU + CF10 combinations showed increased EdU incorporation into DNA, increased double-strand breaks (DSBs), and S-G2/M cell-cycle arrest. Ph

SUBMITTER: Das U 

PROVIDER: S-EPMC12862372 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature