Targeting tumors with hypoxia-activated cytotoxins

This review focuses on the recent development of hypoxia-activated cytotoxins. Such drugs are prodrugs activated to cytotoxic products in the hypoxic environment of solid tumors (so-called bioreductive prodrugs), but can also be activated by radiation (radiation-activated prodrugs). These compounds grew out of research on hypoxic radiosensitizers, which are compounds that can overcome the radiation resistance of hypoxic cells, and we will discuss this area also. The advantages and limitations of each class of the hypoxia-activated cytotoxins are discussed. In addition we will discuss a novel method of targeting drugs to tumors based on anaerobic bacteria, the so-called clostridia-directed enzyme prodrug therapy or CDEPT, which also exploits the hypoxic environment of solid tumors.