5-Fluorotroxacitabine Displays Potent Anti-Leukemic Effects And Circumvents Resistance To Ara-C

Aniket Bankar,Thirushi Piyumika Siriwardena,Biljana Rizoska,Christina Rydergard,Helen Kylefjord,Vilma Rraklli,Anders Eneroth,Pedro Pinho,Stefan Norin,Johan Bylund,Sara Moses,Richard Bethell,Simon Kavanagh,Xiaoming Wang,Rose Hurren,Mark D. Minden,Paul Targett-Adams,Aaron D. Schimmer,Mark Albertella

BLOOD（2018）

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摘要

The cytotoxic nucleoside cytarabine (Ara-C) is a cornerstone of AML induction and consolidation therapies, but drug resistance contributes to disease relapse. Among clinically relevant mechanisms of Ara-C resistance is the over-expression of cytidine deaminase (CDA). CDA degrades Ara-C through deamination into inactive metabolites and its increased expression in AML cells results in drug resistance. Therefore, nucleoside analogues that are not degraded by CDA may be new therapeutic agents for this disease.

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