Attempts to remodel the pathways of gemcitabine metabolism: Recent approaches to overcoming tumours with acquired chemoresistance

Yuriko Saiki, Shuto Hirota, Akira Horii

Research output: Contribution to journalReview articlepeer-review

Abstract

Gemcitabine is a cytidine analogue frequently used in the treatment of various cancers. However, the development of chemoresistance limits its effectiveness. Gemcitabine resistance is regulated by various factors, including aberrant genetic and epigenetic controls, metabolism of gemcitabine, the microenvironment, epithelial-to-mesenchymal transition, and acquisition of cancer stem cell properties. In many situations, results using cell lines offer valuable lessons leading to the first steps of important findings. In this review, we mainly discuss the factors involved in gemcitabine metabolism in association with chemoresistance, including nucleoside transporters, deoxycytidine kinase, cytidine deaminase, and ATP-binding cassette transporters, and outline new perspectives for enhancing the efficacy of gemcitabine to overcome acquired chemoresistance.

Original languageEnglish
Pages (from-to)819-831
Number of pages13
JournalCancer Drug Resistance
Volume3
Issue number4
DOIs
Publication statusPublished - 2020

Keywords

  • ATP-binding cassette transporters
  • Chemoresistance
  • Cytidine deaminase
  • Deoxycytidine kinase
  • Gemcitabine
  • Human equilibrative nucleoside transporter 1
  • Metabolism

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology (medical)

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