Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies.
Ribonucleotide reductases catalyze the de novo biosynthesis of deoxyribonucleosides for DNA synthesis. Increased ribonucleotide reductases activity has been associated with malignant transformation and tumor cell growth. The ribonucleotide reductases inhibitors may bind with the R1 subunit of the enzyme (Class 1) or the nonheme iron (Class 2). This review focuses on the therapeutic use of ribonucleotide reductases inhibitors in hematologic malignancies. Hydroxyurea, fludarabine and cladribine have established roles in the management of hematologic malignancies, while other ribonucleotide reductases inhibitors, such as gemcitabine, tezacitabine and heterocyclic carboxaldehyde thiosemicarbazones (e.g., triapine) are being evaluated in clinical trials.
Tsimberidou
Apostolia-Maria
AM
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston 77030, USA. atsimberidou@mdanderson.org
Alvarado
Yesid
Y
Giles
Francis J
FJ
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D012264:Ribonucleotide Reductases