RATIONALE FOR THE USE OF GENISTEIN-CONTAINING SOY MATRICES IN CHEMOPREVENTION TRIALS FOR BREAST AND PROSTATE-CANCER

Pharmacologists have realized that tyrosine kinase inhibitors (TKI) ha ve potential as anti-cancer agents, both in prevention and therapy pro tocols. Nonetheless, concern about the risk of toxicity caused by synt hetic TKIs restricted their development as chemoprevention agents. How ever, a naturally occurring TKI (the isoflavone genistein) in soy was discovered in 1987. The concentration of genistein in most soy food ma terials ranges from 1-2 mg/g. Oriental populations, who have low rates of breast and prostate cancer, consume 20-80 mg of genistein/day, alm ost entirely derived from soy, whereas the dietary intake of genistein in the US is only 1-3 mg/day. Chronic use of genistein as a chemoprev entive agent has an advantage over synthetic TKIs because it is natura lly found in soy foods. It could be delivered either in a purified sta te as a pill (to high-risk, motivated patient groups), or in the form of soy foods or soy-containing foods. Delivery of genistein in soy foo ds is more economically viable ($1.50 for a daily dose of 50 mg) than purified material ($5/day) and would require no prior approval by the FDA. Accordingly, investigators at several different sites have begun or are planning chemoprevention trials using a soy beverage product ba sed on SUPRO(TM), an isolated soy protein manufactured by Protein Tech nologies International of St. Louis, MO. These investigators are exami ning the effect of the soy beverage on surrogate intermediate endpoint biomarkers (SIEBs) in patients at risk for breast and colon cancer, d efining potential SIEBs in patients at risk for prostate cancer, and d etermining whether the soy beverage reduces the incidence of cancer re currence. These studies will provide the basis for formal Phase I, Pha se II and Phase III clinical trials of genistein and soy food products such as SUPRO(TM) for cancer chemoprevention. (C) 1995 Wiley-Liss, In c.