Clinical aspects of cell death in breast cancer: the polyamine pathway as a new target for treatment

Because intracellular polyamines have a critical role in cell proliferation and death pathways, the polyamine metabolic pathway represents a potential target for intervention in cancers. A number of polyamine analogues have b een identified that downregulate polyamine synthesis and enhance polyamine catabolism, thereby depleting intracellular polyamines. Treatment of human breast cancer cell lines in culture with these analogues has been shown to decrease cell proliferation and induce programmed cell death, Phase I studi es with one analogue are now complete, setting the stage for phase II trial s to determine efficacy, in addition to preclinical studies to examine comb inations of polyamine analogues and conventional cytotoxics.