Saiki Yuriko, Hirota Shuto, Horii Akira
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan.
Office of Medical Education, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan.
Cancer Drug Resist. 2020 Oct 12;3(4):819-831. doi: 10.20517/cdr.2020.39. eCollection 2020.
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.
吉西他滨是一种常用于治疗多种癌症的胞苷类似物。然而，化疗耐药性的出现限制了其疗效。吉西他滨耐药性受多种因素调控，包括异常的基因和表观遗传控制、吉西他滨的代谢、微环境、上皮-间质转化以及癌症干细胞特性的获得。在许多情况下，利用细胞系得出的结果能提供宝贵的经验教训，引领重要发现的第一步。在本综述中，我们主要讨论与化疗耐药性相关的吉西他滨代谢所涉及的因素，包括核苷转运体、脱氧胞苷激酶、胞苷脱氨酶和ATP结合盒转运体，并概述增强吉西他滨疗效以克服获得性化疗耐药性的新观点。
