Mechanisms of anti-cancer action and pharmacology of clofarabine.
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.
Zhenchuk
Anna
A
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institute, Karolinska Hospital, SE-17176 Stockholm, Sweden.
Lotfi
Koroush
K
Juliusson
Gunnar
G
Albertioni
Freidoun
F
D000227:Adenine Nucleotides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001087:Arabinonucleosides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000077866:Clofarabine; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D019337:Hematologic Neoplasms / Q000188:drug therapy; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*
D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine