Mechanisms of anti-cancer action and pharmacology of clofarabine

Research output: Contribution to journalDebate/Note/Editorial

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.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology

Keywords

  • Leukemias, Pharmacokinetics, Resistance to antimetabolites, Apoptosis, reductase, Ribonucleotide, Deoxycytidine kinase, Clofarabine, Nucleoside analogues
Original languageEnglish
Pages (from-to)1351-1359
JournalBiochemical Pharmacology
Volume78
Issue number11
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedNo

Bibliographic 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)