Table 1.

Gemcitabine metabolism-associated chemoresistance entities in pancreatic cancer.

Target Entity	Role in Gemcitabine Metabolism	Resistance Pattern	Impact on Progression of Chemoresistance to Gemcitabine	References
Nucleoside transporters	Drug transport	Downregulation	Level of hEN1, hCNT1 and hCNT3 are correlative of resistance to gemcitabine	[63,64]
Deoxycytidine kinase	Intracellular drug activation	Downregulation	Reduced levels of dCK are linked with acquired resistance to gemcitabine	[65]
Cytidine deaminase	Drug inactivation	Upregulation	CDA induced deamination causes degradation and excretion of gemcitabine	[26]
Ribonucleotide reductase	Competition in DNA synthesis	Upregulation	RR mediates DNA synthesis via generation of dCTPs	[66]
Thymidylate synthase	Competition in DNA synthesis	Upregulation	Regulation of early stages of DNA biosynthesis, activation of salvage pathway	[67,68]