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Commentary: Mechanisms of anti-cancer action and pharmacology of clofarabine: in BIOCHEMICAL PHARMACOLOGY, ISSN 0006-2952, vol 78, issue 11, pp 1351-1359
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
Lund Strategic Center for Stem Cell Biology and Therapy, Department of Hematology, Lund University Hospital, Lund, Sweden.
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
2009 (English)In: Biochemical Pharmacology, ISSN 0006-2952, E-ISSN 1873-2968, Vol. 78, no 11, 1351-1359 p.Article in journal, Editorial material (Other academic) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 78, no 11, 1351-1359 p.
Keyword [en]
Clofarabine, Nucleoside analogues, Deoxycytidine kinase, Ribonucleotide reductase, Apoptosis, Resistance to antimetabolites, Pharmacokinetics, Leukemias
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-51598DOI: 10.1016/j.bcp.2009.06.094OAI: diva2:275952
Available from: 2009-11-09 Created: 2009-11-09 Last updated: 2014-07-01Bibliographically approved

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Lotfi, Koroush
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