The Patrick C. Walsh Prostate Cancer Research Fund
If this Stem Cell Protein is Blocked, Will it Kill Prostate Cancer?
There is a certain pronoun with an alphabetical name, called NF-ĸB (the funny-looking “ĸ” is pronounced “Kappa”). NF-ĸB is commonly active in prostate cancer, especially in stem cells within a tumor. “NF-ĸB helps a prostate tumor grow by increasing the expression of genes that inhibit cell death,” explains scientist Alan Friedman, M.D., a 2012 recipient of funding from the Patrick C. Walsh Prostate Cancer Research Fund.
This protein is activated through the action of a classic signaling pathway, and several groups are working to determine whether blocking this pathway would help slow cancer growth. But Friedman and colleague Ido Paz-Priel, M.D., have identified another pathway that also causes NF-ĸB to start its unwelcome activity. This pathway is controlled by another protein, called C/ EBP, and Friedman and Paz-Priel believe that blocking this pathway – either by itself, or with the other pathway – may be effective in preventing the rampant growth of prostate cancer.
“We are working to determine the importance of C/EBP-mediated NF-ĸB activation for the survival of prostate cancer cells,” says Friedman. In laboratory experiments, they are blocking C/EBP in several prostate cancer cell lines and looking to see “whether this leads to their death.” Another important question, which they hope to answer: Does lowering production of the C/ EBP protein make prostate cancer cells easier to kill by chemotherapy, by radiation, or by drugs that inhibit the classic pathway of NF-ĸB activation? Friedman and Paz-Priel are looking for answers to these questions in prostate cancer cells, and also in prostate cancer stem cells. “Through these experiments, we hope to validate the interaction of C/EBP and NF-ĸB as an important therapeutic target,” Friedman says. The team also is working to develop drugs designed to disrupt this interaction. “In the longterm, we envision evaluating their ability to contribute to the cure of prostate cancer.”