Thomas T. Anderson, PhD

It has long been known that pregnancy is associated with a decreased risk of breast cancer. We have estimated that, if short-term administration of a drug to at-risk women would decrease their risk of breast cancer to the same extent as would the experience of pregnancy, then we could prevent as many as 50,000 cases of breast cancer every year. Alpha-fetoprotein (AFP), a protein produced by the fetal liver, is one of the agents of pregnancy that leads to a significant reduction in risk of acquiring breast cancer for women who experience term pregnancy. AFP stops the growth of estrogen-dependent human breast cancer tumors (xenografts) that have been transplanted to immune-deficient mice. AFP is non-toxic and its mechanism of action is different from that of agents currently used in the clinic to treat breast cancer, but it wouldn’t be a very good drug because it is too large. We have designed a novel cyclic synthetic peptide, AFPep, which mimics the active site of AFP. AFPep inhibits the growth of human breast cancer cells in culture and in xenografts in mice. AFPep has a novel mechanism of action, one that is different from that of tamoxifen; in fact, AFPep is active even against tamoxifen-resistant forms of breast cancer. Recently, we have shown that AFPep can prevent cancer when administered to animals that have been exposed to a potent carcinogen. Pre-clinical studies are designed to develop this molecule into a pharmaceutical agent useful for the prevention and treatment of human breast cancer. (Cancer prevention models and toxicity models are used.) We continue to develop specialty analogs of AFPep that have important and desirable properties such as being active after oral administration (design and synthesis of peptides is the major technique). Investigations of mechanism of action include cell culture studies to investigate signaling pathways. We want to investigate whether AFPep will prevent cancers that are induced by natural hormones or those that are induced by radiation (i.e., dirty bomb levels of radiation).