News Release

Jefferson scientists find molecular markers to predict prostate cancer relapse

Peer-Reviewed Publication

Thomas Jefferson University

Cancer researchers at Jefferson Medical College have found two potential molecular biomarkers that may predict the effectiveness of therapy for prostate cancer and the potential for relapse following radiation therapy. Researchers, led by Bruce Turner, M.D., Ph.D., assistant professor of radiation oncology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and John C. Reed, M.D., Ph.D., scientific director of the Burnham Institute in La Jolla, examined the levels of proteins called IAPs (Inhibitors of Apoptosis), which prevent cell suicide, or apoptosis. Their activity increases when cells become cancerous, he explains, as cells continue to proliferate and grow, a hallmark of cancer.

The researchers focused on two IAPs: cIAP-1 and XIAP. They identified 65 men with early stage prostate cancer treated with radiation therapy and who were followed for more than five years. They obtained a tumor sample from each patient.

They found that there were increasingly higher levels of both proteins as patients "went from benign prostate epithelium to a precancerous stage to prostate cancer as compared to the normal prostate epithelium," Dr. Turner says.

"We demonstrated for the first time that these proteins are up-regulated in prostate cancer and may be accurate biomarkers of response to therapy," he says. They also found that alterations in the levels of both of these proteins "correlated with predicting distant metastasis-free survival." Dr. Turner presents the findings May 22 at the annual meeting of the American Society of Clinical Oncology in New Orleans.

"These findings have the potential to come up with biomarkers for prostate cancer because the disease cancer has very few molecular markers that predict response to therapy," Dr. Turner says. "Breast cancer, for example, has markers such as estrogen/progesterone receptors, p53 and HER2-neu. Perhaps the IAPs may be useful molecular markers that will help guide clinical decision-making." For prostate tumors that were cIAP-1 positive, the researchers found that five-year distant metastasis-free survival was 47 percent. However, in those samples that were cIAP-1 negative, five-year distant metastasis-free survival was 84 percent. In contrast, for those patients whose samples were XIAP positive, the distant metastasis-free survival was 81 percent versus only 51 percent for those who were negative.

The researchers didn't see differences in overall survival between the groups, which is probably due to the long survival of prostate cancer patients treated with modern therapy, Dr. Turner says.

"The IAP proteins are up-regulated, and altered levels of cIAP-1 and XIAP are useful as biomarkers to predict response to therapy and distant metastasis-free survival." Both proteins may be targets for future drug development.

Dr. Turner notes that some patients had altered levels of the proteins and didn't develop metastatic disease. "There are many different pathways regulating the development of prostate cancer and perhaps the IAPs are one major pathway," he says. "Elevated cIAP-1 protein levels within the prostate tumor don't necessarily mean you will develop metastatic disease, but clearly those with higher levels of cIAP-1 as opposed to having low levels, according to our findings, appear to be at increased risk of developing metastatic disease."

Next, Dr. Turner would like to evaluate these proteins in a larger group of patients treated with radiation and those treated with a radical prostatectomy, or removal of the prostate gland, and with long-term followup to better define correlations between metastatic disease and long-term survival.

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