Pathway Gemcitabine Pathway, Pharmacodynamics

Cancer cell
Model non-tissue specific cancer cell displaying genes which may be involved in the gemcitabine pathway.
Gemcitabine Pathway, Pharmacodynamics
clickable pathway icons

Description

Gemcitabine (2',2'-difluorodeoxycitidine) is a difluorinated nucleoside analog. It is delivered as a prodrug that requires intracellular transport and phosphorylation to exert its cytotoxic effects and acts specifically during S-phase of the cell cycle.

This diagram shows the action of gemcitabine on a generic cancer cell. The diphosphate form is a potent inhibitor of ribonucleotide reductase (coded for by the genes RRM1, RRM2 and RRM2B) leading to perturbations in the deoxynucleotide pools, while the active triphosphate form is incorporated into DNA, resulting in interference with DNA chain elongation and disruption of cell growth.

Authors: CF Thorn, JH Gray, KM Giacomini.
Citation:
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
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History:
Therapeutic Categories:
  • Anticancer agents

Entities in the Pathway

Genes (10)

Drugs/Drug Classes (1)

Relationships in the Pathway

Arrow FromArrow ToControllersPMID
DCK DCK dNTPs
RRM1, RRM2, RRM2B RRM1, RRM2, RRM2B gemcitabine
dNDPs dNTPs
gemcitabine gemcitabine DCK 14514691
gemcitabine gemcitabine NT5C
gemcitabine gemcitabine CMPK1
gemcitabine gemcitabine
NDPs dNDPs RRM1, RRM2, RRM2B
dNTPs dNTPs
gemcitabine gemcitabine SLC28A1, SLC28A3, SLC29A1 10547395
gemcitabine gemcitabine

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