Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies

Abstract

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.