Between 1970 and 1994, cancer claimed the lives of about 0.5 million Americans every year. According to the most recent statistics, it is estimated that approximately 1.3 million new cases of cancer will be diagnosed and 555,500 people will die from cancer in the United States in the year 2002. Despite these statistics, 5-year survival rates following diagnosis stand at around 55%, and for some specific cancers such as breast and prostate cancer this figure is very much higher. Development of molecules able to prevent metastasis should cause further dramatic improvements in life expectancy. Increased cellular activity of ornithine decarboxylase, the first and rate-limiting enzyme in polyamine synthesis, is an independent adverse prognostic factor for overall survival in human breast cancer, thus suggesting an important role for polyamines in tumor progression. Depleting polyamine pools has already been shown to provoke impressive proapoptotic activity in breast cancer cells however Italian researchers have now shown that this strategy can also prevent metastasis. Irreversible inhibition of ornithine decarboxylase, significantly reduced, in a dose-dependent manner, the invasiveness in matrigel of highly invasive breast cancer cells by approximately 70 and likewise blocked 'stellate' colony formation (an indicator of aggressive phenotype). Oral administration of the same ornithine decarboxylase inhibitor reduced the growth rate of breast cancer tumors in nude mice. Strikingly, although ornithine decarboxylase inhibition had little effect on reducing local invasion, the formation of pulmonary metastasis was nearly totally abolished. These results suggest that ornithine decarboxylase inhibitors should not only prevent tumor growth but that such molecules should also be able to prevent metastatic progression even in the event that cells escape the environment of the primary tumor. Despite this potential, to our knowledge only 3 ornithine decarboxylase inhibitors are in development or on the market and only one of these is being investigated for the treatment of cancer. This exciting target thus deserves further pharmaceutical attention.

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