Recent developments to improve the efficacy of cytotoxic nucleoside analogues.

Cytotoxic nucleoside analogues are clinically important anticancer drugs. The newer member of this family, gemcitabine, has shown great activity in solid tumors and thus enlarged the spectra of malignancies treated by this family of molecules. However, the clinical use of nucleoside analogues is limited by important side-effects and primary or acquired drug resistance, and there is an unmet medical need for the development of new molecules and technologies allowing a suitable treatment of cancer patients with these agents. In this article we will review literature data and patents concerning (i) the recent development of some novel nucleoside analogues, (ii) oral formulations for cytotoxic nucleoside analogues, (iii) strategies to circumvent acquired resistance to nucleoside analogues, and (iv) gene therapy strategies used to increase cytotoxicity of nucleoside analogues.