ABSTRACT
Gallium salts have been explored for their applicability as antineoplastic drugs for more than two decades, but clinical experience has revealed unfavorable pharmacokinetic and toxicological properties. This chapter gives a short overview of the current status of other main group metal compounds in cancer therapy and anticancer drug development. More recently, antimitotic properties similar to those of vinca alkaloids have been proposed as a relevant component of the antitumor activity of gallium. Gallium is taken up into transferrin receptor-expressing cells mainly by the transferrin receptor-mediated pathway. Several mechanisms of action involving inhibition of signal transduction pathways, interaction with glutathione-related enzymes and interference with mitotic microtubule assembly are discussed. Synergistic effects have been reported for combinations of simple gallium salts or transferrin-bound gallium with various cell cycle phase-specific antineoplastic agents in vitro. The development of orally available gallium complexes aims at improving the therapeutic potential of gallium primarily by altering its pharmacokinetic properties.
