Tracking the path of a deadly disease

Researchers in the Department of Biological Sciences are part of a collaborative project to study the ways in which prostate cancer spreads to bones.

The National Cancer Institute has awarded a $7.6 million grant to the research, which involves several institutions of higher education across the country. UD's part of the study is led by Mary C. Farach-Carson, professor of biological sciences, who says the project has important implications for the pathways and mechanisms that lead prostate cancer to metastasize, or spread, to the bones in some patients.

"I am delighted to have this opportunity to participate in a project of such importance," she says. "This is an outstanding collaborative team because it brings researchers with a longstanding expertise in prostate cancer together with our group, which has expertise in bone, the principal site of metastasis of prostate cancer."

Many people with cancer develop bone metastasis at some point in the course of their disease, according to the American Cancer Society, with cancers of the prostate, breast, lung, kidney and thyroid most likely to spread to the bones.

Farach-Carson notes that great strides have been made in the ability of medical science to treat cancer in its early stages. For example, she says, patients whose prostate cancer is detected before it has spread beyond the prostate itself have a five-year survival rate of virtually 100 percent. After the cancer has spread to the bone, that survival rate falls to 34 percent.

"It's a completely different prognosis if it's detected at the later stages," Farach-Carson says. "That's why there's such an emphasis on early detection."

That difference also is why the research project is utilizing an interdisciplinary approach, she says. Researchers at Emory University, led by Leland Chung, director of urological research at the Atlanta university and head of the collaborative project, recognized the need to look at bone biology in studying prostate cancer and brought the UD team on board. Farach-Carson, who joined the UD faculty in 1998, specializes in research on bones and has worked with such disorders as osteoporosis.

Chung says that nearly 90 percent of all prostate cancer patients who die from the disease experience bone metastasis.

"The ultimate goal of this project," he says, "is to develop novel diagnostic, prognostic and treatment options based on a better understanding of the mechanics of prostate cancer and bone metastasis."

And, because breast cancer also metastasizes to bone, "our findings should have broad implications in that arena as well," Farach-Carson says.

Carlton Cooper and Robert Sikes, both assistant professors of biological sciences at UD, also work in the area of prostate cancer and are involved in the research. The Delaware group includes graduate and undergraduate research assistants as well, and the team meets regularly in person and via web conferencing with the Emory group.

The National Cancer Institute funding, combined with statewide initiatives to address Delaware's high cancer mortality rate and the 2002 opening of the Helen F. Graham Cancer Center at Christiana Hospital near Newark, Del., makes the timing right for focusing on such research projects, Farach-Carson says. The grant, she says, "is a really good thing for our research and for Delaware."

The three primary projects that make up the collaboration are

• A study of the biology of tumor-stroma interaction, which will be led by Chung. This project will study the interaction between metastatic human prostate cancer cells and bone or prostate stroma, which contributes to localized cancer growth, invasion and distant metastasis. The purpose is to develop potential molecular or genetic targeting strategies for treatment of prostate cancer bone metastasis;
  
  
• A study of heparan sulfate proteoglycans in prostate cancer bone metastasis, which will be led by Farach-Carson. This research will explore the interactions between prostate cancer cells and the marrow stromal cells that facilitate the progression of metastases in bone and bone marrow. By better understanding the bone stromal microenvironment, researchers predict a better understanding of how metastasis occurs within the bone, which they say could lead to the development of novel therapeutic strategies for disrupting that process; and
  
  
• A study of mitochondrial DNA mutations in prostate tumorigenesis and stromal and epithelial interaction, which will be led by John Petros, associate professor of urology at Emory. This project will research mitochondrial DNA mutations in prostate cancer to determine how those mutations protect cancer cells from their normal cell death and enhance tumor growth and metastasis and how cancer-associated stromal cells may support the survival of cancer cells.

Chung says an important goal of the three projects is to discover relevant genes that may "turn on or turn off" during the making of prostate cancer cells and their subsequent metastasis to bone.

"By embarking on this team approach to the problem of prostate cancer bone metastasis, we may discover new pathways that support the metastasis," he says. "As a result, new therapies may be generated in the diagnosis and treatment of men with advanced forms of prostate cancer."

Chung says the strength of the project is its interactive nature. "We are all looking at different parts of the metastasis problem, and the laboratory activity is highly interactive," he says. "This project is organized to achieve synergy among individual scientists who have an established track record of research collaboration."

In addition to several units at Emory and the UD researchers, other team members in the collaboration are from the University of Virginia, Stanford University and the Fred Hutchinson Cancer Research Center.

--Neil Thomas, AS '76