Barakat: Making cancer more susceptible to chemotherapy
Advanced prostate cancer is difficult to treat because it's resistant to chemotherapy, radiation therapy, and hormonal therapy. "We need a better understanding of the underlying mechanisms in advanced disease," says postdoctoral fellow David Barakat, Ph.D. Working with two oncologists, Alan Friedman, M.D., and Ido Paz-Priel, M.D., he is studying a family of proteins called C/ EBPs, which control cell growth. "We previously found that C/EBPs, in cooperation with another protein, block cell death by increasing the expression of certain prosurvival genes," says Barakat.
Now the scientists have shown that one form of this protein, called C/EBP beta, is made in prostate cancer cells – and that when it is suppressed, the cancer is more susceptible to chemotherapy. In laboratory studies, when C/EBP beta is reduced, prostate cancer cells are less able to form new colonies, "further indicating a critical role for C/EBP beta in prostate cancer cell survival." Their work also suggests that C/EBP is increased in men who are undergoing hormonal therapy. "We think that up-regulation of C/EPB beta is a resistance mechanism that allows prostate cancer cells to survive androgen deprivation," says Barakat. It may be that blocking this protein will make hormonal therapy more effective, as well.