ABSTRACT
This chapter evaluates the metabolic and pharmacodynamic characteristics of anticancer nucleoside analogs of major importance. It utilizes an understanding of the pharmacology and mechanisms of action of the nucleosides as rationales for the design of combinations with other anticancer drugs or modalities such as radiation. Specific nucleoside transport systems provide the major pathway for nucleoside analogs to cross the plasma membrane and gain access to cells. The lowered level of DNA synthesis caused by the combination therapy was maintained until the next infusion of cytarabine. The ability to accumulate and retain nucleotide analogs varies widely among cell lines. It is assumed that this directly reflects the specific activities of the various enzymes involved with the phosphorylation, dephosphorylation, and metabolic clearance of the compounds. The actual active metabolites of these nucleoside analogs are the nucleoside monophosphates once they have become incorporated into the terminus of the elongating DNA strand.
