Mechanisms of anti-cancer action and pharmacology of clofarabine

Anna Zhenchuk, Koroush Lotfi, Gunnar Juliusson, Freidoun Albertioni

    Research output: Contribution to journalDebate/Note/Editorial

    77 Citations (SciVal)

    Abstract

    Clofarabine, a next-generation deoxyadenosine analogue, was developed on the basis of experience with cladribine and fludarabine in order to achieve higher efficacy and avoid extramedullary toxicity. During the past decade this is the only drug granted approval for treatment of pediatric acute leukemia. Recent clinical studies have established the efficacy of clofarabine in treating malignancies with a poor prognosis, such as adult, elderly, and relapsed pediatric leukemia. The mechanisms of its anti-cancer activity involve a combination of direct inhibition of DNA synthesis and ribonucleotide reductase and induction of apoptosis. Due to this broad cytotoxicity, this drug is effective against various subtypes of leukemia and is currently being tested as an oral formulation and for combination therapy of both leukemias and solid tumors. In this review we summarize current knowledge pertaining to the molecular mechanisms of action and pharmacological properties of clofarabine, as well as clinical experiences with this drug with the purpose of facilitating the evaluation of its efficacy and the development of future therapies. (C) 2009 Elsevier Inc. All rights reserved.
    Original languageEnglish
    Pages (from-to)1351-1359
    JournalBiochemical Pharmacology
    Volume78
    Issue number11
    DOIs
    Publication statusPublished - 2009

    Bibliographical note

    The information about affiliations in this record was updated in December 2015.
    The record was previously connected to the following departments: Hematology/Transplantation (013022014)

    Subject classification (UKÄ)

    • Hematology

    Keywords

    • Leukemias
    • Pharmacokinetics
    • Resistance to antimetabolites
    • Apoptosis
    • reductase
    • Ribonucleotide
    • Deoxycytidine kinase
    • Clofarabine
    • Nucleoside analogues

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