DNA synthesis pathway via incorporation of trifluridine into DNA

The "DNA synthesis pathway via incorporation of trifluridine into DNA" is not a single molecular target but rather describes the mechanism by which the nucleoside analogue drug **trifluridine** exerts its antitumor effects. Trifluridine is phosphorylated within cells to its active triphosphate form and becomes incorporated into newly synthesized nuclear or viral DNA in place of thymidine. This misincorporation disrupts normal base pairing during replication, resulting in defective or dysfunctional genetic material that impairs cell proliferation. In cancer therapy—particularly with the combination drug TAS‑102/Lonsurf—this leads to **replication stress**, activation of cell cycle checkpoints such as p53-p21 signaling, G2 phase arrest, cellular senescence if p53 is functional, or apoptotic death if p53 is lost. The same mechanism underlies both antitumor efficacy and dose-limiting hematologic toxicities such as myelosuppression due to effects on rapidly dividing bone marrow progenitors. While this process can be described as a "pathway," it does not correspond to an individual protein target like an enzyme or receptor but rather represents the cumulative effect on cellular machinery involved in **DNA replication**.[1][2][3][4][5]

Other names

Trifluridine incorporation into DNATrifluridine-mediated DNA synthesis inhibitionFTD-induced DNA replication stress pathway

Incorporation of trifluridine triphosphate into replicating DNA in place of thymidine, leading to defective or dysfunctional DNA and inhibition of cell proliferation[1][3] Reversible inhibition of thymidylate synthase by trifluridine monophosphate, further disrupting dTTP pools required for normal DNA synthesis[4]