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Veliparib + floxuridine is an investigational combination therapy consisting of the PARP inhibitor veliparib and the antimetabolite floxuridine. Veliparib (ABT-888) is a small molecule inhibitor of PARP-1 and PARP-2, enzymes critical for the repair of single-strand DNA breaks via the base excision repair pathway. Inhibition of PARP leads to the accumulation of DNA damage and cell death, particularly in tumors with homologous recombination deficiencies. Floxuridine is a pyrimidine analog that is converted to 5-fluorodeoxyuridine monophosphate, a potent inhibitor of thymidylate synthase, which is essential for DNA synthesis. This combination is being studied for its potential synergistic effects in treating advanced epithelial ovarian, primary peritoneal, and fallopian tube cancers, where the inhibition of DNA repair by veliparib may sensitize tumor cells to the DNA-damaging effects of floxuridine.
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