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Mechanisms of anti-cancer action and pharmacology of clofarabine

Zhenchuk, Anna; Lotfi, Koroush; Juliusson, Gunnar LU and Albertioni, Freidoun (2009) In Biochemical Pharmacology 78(11). p.1351-1359
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... (More)
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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Leukemias, Pharmacokinetics, Resistance to antimetabolites, Apoptosis, reductase, Ribonucleotide, Deoxycytidine kinase, Clofarabine, Nucleoside analogues
in
Biochemical Pharmacology
volume
78
issue
11
pages
1351 - 1359
publisher
Elsevier
external identifiers
  • wos:000271069600001
  • scopus:70349771790
ISSN
0006-2952
DOI
10.1016/j.bcp.2009.06.094
language
English
LU publication?
yes
id
3f8f4f07-aa0c-44b6-890c-d8d598d58362 (old id 1505841)
date added to LUP
2009-11-24 10:27:10
date last changed
2017-10-22 03:40:59
@misc{3f8f4f07-aa0c-44b6-890c-d8d598d58362,
  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.},
  author       = {Zhenchuk, Anna and Lotfi, Koroush and Juliusson, Gunnar and Albertioni, Freidoun},
  issn         = {0006-2952},
  keyword      = {Leukemias,Pharmacokinetics,Resistance to antimetabolites,Apoptosis,reductase,Ribonucleotide,Deoxycytidine kinase,Clofarabine,Nucleoside analogues},
  language     = {eng},
  number       = {11},
  pages        = {1351--1359},
  publisher    = {Elsevier},
  series       = {Biochemical Pharmacology},
  title        = {Mechanisms of anti-cancer action and pharmacology of clofarabine},
  url          = {http://dx.doi.org/10.1016/j.bcp.2009.06.094},
  volume       = {78},
  year         = {2009},
}