Pyrimidine nucleoside analogs in cancer treatment.

Pyrimidine nucleoside analogs are essential components of hematological malignancy therapy and are also used in the treatment of solid tumors. These agents act as antimetabolites, compete with physiologic pyrimidine nucleosides and, consequently, interact with a large number of intracellular targets to induce cytotoxicity. Pyrimidine nucleoside analogs share some common characteristics, such as requiring both transport by specific membrane transporters and intracellular metabolism. However, these compounds differ in regards to their preferential interaction with certain targets, which may explain why some compounds are more effective against rapidly proliferating tumors and others against neoplasias with a more protracted evolution. Recent progress in the identification and characterization of nucleoside transporters and the enzymes of nucleoside metabolism, as well as an understanding of the molecular mechanisms of anticancer nucleoside activity, provides opportunities for the development of new pyrimidine nucleoside analogs. Strategies to optimize intracellular analog accumulation and to enhance cancer cell selectivity are proving beneficial in clinical trials.