Nucleic acid metabolism: the key therapeutic target for myeloid tumors
Tomohiro Yabushita, Susumu Goyama
Abstract
• The de novo nucleotide biosynthesis pathway is a key therapeutic target for myeloid tumors. • Nucleoside analogs, especially pyrimidine analogs, remain the mainstay of treatment for myeloid tumors. • Drugs that target the de novo nucleotide biosynthesis pathway, such as IMPDH inhibitors, show promise in the treatment of myeloid tumors. Nucleic acid analogs, including cytarabine, decitabine, and azacitidine, have significantly advanced therapeutic approaches for myeloid tumors over the past five decades. Nucleic acid metabolism is a crucial pathway driving myeloid tumorigenesis, with emerging evidence indicating that myeloid tumors are particularly dependent on the de novo nucleotide synthesis pathway, underscoring its potential as a therapeutic target. This review provides a comprehensive overview of nucleic acid metabolism, with a particular focus on de novo nucleotide synthesis. We then describe the range of clinically utilized agents targeting nucleic acid metabolism and discuss our recent findings on the non-epigenetic actions of decitabine, as well as the therapeutic effects of IMPDH inhibitors in the treatment of myeloid tumors.