Interference with polyamine biosynthesis and/or function by analogs of polyamines or methionine as a potential anticancer chemotherapeutic strategy.

The obvious goal in cancer chemotherapy is selectivity. Highly cytotoxic agents abound but their usefulness as anticancer agents extends only so far as their specificity for tumor cells and tissues. In this context, we have reviewed those aspects of polyamine and AdoMet metabolism and function which might contribute to their potential as target sites for chemotherapeutic intervention. Although largely untested to date and far from unequivocal, these various considerations seem to provide sufficient rationale for continued evaluation of the therapeutic potential of these sites. Polyamine analogs and methionine analogs designed to modulate polyamine biosynthesis directly or through AdoMet formation have been discussed as strategies to effect this goal and previous studies with similar analogs have been reviewed. Progress achieved thus far with analogs derived from our own laboratories provides novel insights into polyamine and AdoMet metabolism and/or function as well as new leads towards the design of more effective agents and drug combinations. More detailed reading of the biochemistry of polyamines in eukaryotes and prokaryotes is available in several very excellent current reviews (6-9, 77).