Gemcitabine-incorporated DNA

Gemcitabine-incorporated DNA is not a physiologic target itself but rather the molecular outcome of gemcitabine (2',2'-difluorodeoxycytidine) treatment. Gemcitabine is a prodrug that enters cells via nucleoside transporters and is phosphorylated to the active triphosphate form (dFdCTP), which is incorporated into nascent DNA. This incorporation results in a phenomenon called "masked chain termination," where one additional nucleotide is added after gemcitabine, but DNA polymerase can no longer extend the DNA, and the usual proofreading exonuclease is unable to remove the analog. This irreversibly halts DNA synthesis, causes S-phase cell cycle arrest, and leads to apoptotic cell death in proliferating tumor cells[3][5][8]. The process also potentiates the effects of certain chemotherapeutics, such as cisplatin, by increasing DNA adduct formation and cytotoxicity[7]. As such, this phenomenon reflects a mechanism of action, not a distinct cellular molecular target.

Other names

dFdC-modified DNAGemcitabine-DNA adduct

Incorporation of gemcitabine triphosphate (dFdCTP) into DNA, causing "masked chain termination" and inhibition of DNA polymerase[3][8]. Inhibition of ribonucleotide reductase (by diphosphate metabolite dFdCDP), further depleting deoxynucleotide pools needed for DNA synthesis[2][5].