Equilibrative nucleoside transporter 1 (hENT1) (hENT1)

Equilibrative nucleoside transporter 1 (hENT1), encoded by the SLC29A1 gene, is a transmembrane protein that facilitates the bidirectional transport of purine and pyrimidine nucleosides across the plasma membrane (UniProt: Q99808). It is the primary transporter responsible for the cellular uptake of gemcitabine, a nucleoside analog used extensively in the treatment of pancreatic and biliary tract cancers (PubMed: 15150567). The specific interaction involving axitinib and gemcitabine represents a significant pharmacodynamic challenge in clinical oncology. Axitinib, a tyrosine kinase inhibitor, has been shown to potently inhibit hENT1 activity at clinically relevant concentrations (PubMed: 22491986). This inhibition prevents gemcitabine from entering target tumor cells, thereby reducing its cytotoxic efficacy and potentially leading to treatment failure. Because of this role, hENT1 expression levels are frequently utilized as a predictive biomarker for gemcitabine response in patients. The co-administration of hENT1 inhibitors like axitinib or erlotinib is a critical safety consideration when designing combination chemotherapy regimens. Beyond drug transport, hENT1 regulates endogenous adenosine levels, which influences cardiovascular function and neurotransmission.

Other names

SLC29A1Solute carrier family 29 member 1ENT1Nucleoside transporter 1

Facilitated diffusion of nucleosides and nucleoside analog drugs across the plasma membrane.