It is the elusive brass ring for scientists seeking better ways to kill prostate cancer — a drug that kills only the cancerous cells, but leaves normal cells unscathed. “Creating drugs that do this is very difficult,” says Prakash Kulkarni, Ph.D., the Irene and Bernard L. Schwartz Scholar. “Certain genes that are overexpressed in cancer cells are usually identical to those made in normal cells; or, if they have mutated, the difference is very subtle.” But one, called PAGE4 (for “P. Antigen Family Member 4), a Cancer/Testis Antigen, is made only by the prostate and the testis. It is “remarkably prostate-specific,” Kulkarni says, and it is present in prostate cancer.
Kulkarni believes that PAGE4 plays an important role in the formation of prostate cancer, and that it represents an ideal target for killing cancerous cells. He and colleagues are studying PAGE4 in both prostate cancer that responds to hormones, as well as in aggressive disease that does not respond to hormones. They are also working to develop a specific assay that will allow them to search for small molecules specific for PAGE4 in libraries of chemical compounds, studying thousands of cells at once. The goal, Kulkarni says, is to develop a drug that will help thwart PAGE4. “This could have a significant impact on the management of prostate cancer.”