RADIOSENSITIZING NUCLEOSIDES

Chemotherapeutic drugs that perturb nucleotide metabolism have the pot ential to produce substantial sensitization of tumor cells to radiatio n treatment, The process is called radiosensitization, and the agents that induce it are called radiosensitizers. The clinical effectiveness of fluoropyrimidines as radiosensitizers has been proven in multiple randomized trials, Thymidine analogues and hydroxyurea also appear to produce clinically relevant increases in radiation sensitivity, Recent laboratory investigations have identified difluorodeoxycytidine (gemc itabine) and fludarabine as promising agents to use in combination wit h radiation, Until recently, little was known about how the biochemica l changes caused by these drugs produced radiosensitization, However, advances in related fields, such as cell cycle checkpoint control, hav e permitted the development of a hypothesis that may explain the relat ive tumor selectivity of fluoropyrimidine-mediated radiosensitization, In addition, recent findings suggest that the rational manipulation o f drug administration schedules and the use of combinations of radiose nsitizers have the potential to improve the efficacy of the currently used agents and to establish the benefit of new ones.