The Sound of Evolution
Gemcitabine
Mechanism of action:
Gemcitabine is a deoxycytidine nucleoside analog. After entering the cell, gemcitabine is first phosphorylated by deoxycytidine kinase into gemcitabine monophosphate (dFdCMP), and is then converted into dFdCDP and dFdCTP. dFdCDP inhibits ribonucleotide reductase, reducing the production of deoxynucleotides (dNTPs), while dFdCTP competes with dCTP and is incorporated into newly synthesized DNA. The final result is impaired DNA replication and accumulation of DNA damage, which activates cell cycle arrest and apoptotic pathways.
Reference(s):
1. Noble S et al. (1997). Gemcitabine. A review of its pharmacology and clinical potential in non-small cell lung cancer and pancreatic cancer. Drugs.
2. Toschi L et al. (2005). Role of gemcitabine in cancer therapy. Future Oncol.
3. Ciccolini J et al. (2016). Pharmacokinetics and pharmacogenetics of gemcitabine as a mainstay in adult and pediatric oncology: an EORTC-PAMM perspective. Cancer Chemother Pharmacol.