Haematologica Reports 2005; 1(issue 8):
99-102[prev][index][next]
The developing role of clofarabine in acute
leukemias
Faderl S
Department of Leukemia, The University of Texas MD Anderson Cancer
Center,
Houston, Texas, USA
Nucleoside analogs count among the most active components of
anticancer therapies.1,2 Through DNA incorporation and
inhibition of ribonucleotide reductase (RnR), an enzyme involved in
the recycling of the celluar nucleotide pool, their effects result
in termination of DNA chain elongation, inhibition of DNA
synthesis, interference with DNA repair mechanisms, and finally
apoptosis.3,4 Several nucleoside analogs have become an
integral part of treatment for a diverse range of malignancies.
Cytarabine (1-β-D-arabinosylcytosine, ara-C) is used
predominantly for therapy of patients with acute myeloid leukemias
(AML) whereas the main spectrum of activity of gemcitabine
(2’,2’-difluorodeoxycytidine), is in solid tumor
malignancies.5,6 Fludarabine
(9-β-D-arabinofuranosyl-2-fluoro-adenine
5’-monophosphate) and cladribine (2-chlorodeoxyadenosine,
2-CdA) have been among the first clinically useful purine
nucleoside analogs and both are highly active in indolent
lymphoproliferative disorders.7 An intriguing aspect of
nucleoside analogs thus remains how apparently minor alterations in
structure can result in major differences with respect to
pharmacology, metabolism, and spectrum of activity. [>Read full article in PDF]
