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OCTN1 Is a High-Affinity Carrier of Nucleoside Analogues

Christina D Drenberg1, Alice A Gibson1, Stanley B Pounds2

  • 1Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio.

Cancer Research
|February 18, 2017
PubMed

Insights

Low expression of the ergothioneine transporter OCTN1 (equilibrative nucleoside transporter 1) predicts poor survival in acute myeloid leukemia (AML) patients treated with cytarabine, indicating its role in nucleoside drug resistance.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Resistance to nucleoside analogues is a significant challenge in cancer therapy.
  • Reduced drug uptake via nucleoside transporters is a proposed mechanism for resistance.
  • The specific transporters involved in resistance to cytarabine in acute myeloid leukemia (AML) are not fully understood.

Purpose of the Study:

  • To investigate the role of nucleoside transporters in cytarabine resistance in AML.
  • To identify specific transporters whose expression levels correlate with patient survival and treatment response.

Main Methods:

  • Transcriptomic profiling of AML patient cohorts.
  • Cell biological studies to confirm transporter function and drug uptake.
  • Analysis of patient survival data in relation to transporter gene expression.

Main Results:

  • Low expression of the ergothioneine transporter OCTN1 (SLC22A4) was found to strongly predict poor event-free and overall survival in AML patients treated with cytarabine.
  • OCTN1 was confirmed to mediate the transport of cytarabine and related cytidine analogues (e.g., gemcitabine) via a saturable process.
  • This transport is sensitive to classic nucleoside transporter inhibitors.

Conclusions:

  • OCTN1 expression is a predictive biomarker for cytarabine treatment outcomes in AML.
  • Targeting OCTN1-mediated transport may offer a strategy to overcome nucleoside analogue resistance.
  • These findings have implications for improving patient survival in various cancers treated with nucleoside analogues.

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