Today's News

Wednesday, March 15, 2000

OREF honors basic research on pathway in fibromatosis

The OREF Clinical Research Award will be presented to Benjamin A. Alman, MD, and Jay S. Wunder, MD, for basic research that will likely lead to novel and improved treatment methods for patients with aggressive fibromatosis. Conventional treatment, which includes surgery, chemotherapy, and radiation therapy, is not consistently effective.

Dr. Alman explained that the fields of developmental biology and molecular oncology have recently become intertwined because research has shown that many genes involved in developmental signaling pathways are also tumor suppressor genes and oncogenes. "An agent that blocks a developmental pathway that is active in a neoplastic process might be an effective chemotherapeutic agent," he said.

Dr. Alman is an assistant professor and scientist in the Division of Orthopaedic Surgery and Program in Developmental Biology at the Hospital for Sick Children and the University of Toronto. Dr. Wunder is assistant professor at the University of Toronto and associate director of the University Musculoskeletal Oncology Unit.

For their study, the research team obtained tissue samples of aggressive fibromatosis from 42 patients who had undergone surgical removal of their tumors as well as samples of the patients' normal tissue for comparison. The tissues were analyzed in a series of experiments to determine the status of DNA, RNA, immunohistochemistry values and identification of mutations.

"We found that aggressive fibromatosis contains mutations in genes that activate a cellular pathway called wingless (or WNT)," reported Dr. Alman and Dr. Wunder. "Activation of this pathway turns on a number of genes in aggressive fibromatosis, including one called cyclooxygenase-two. As more is learned about the role of mediators in the signaling cascade and the downstream genes that regulate proliferation, more effective therapeutic approaches may be devised, based on blockade of this signaling pathway," reported the Canadian team.

The researchers also are trying to determine which genes are regulated by wingless signaling in aggressive fibromatosis so they can identify additional genes that could be regulated by pharmacologic agents that might provide better treatment for this tumor.

Many of the pathways that they have identified to modulate cell behavior in aggressive fribromatosis may also be used to treat some other conditions, said Dr. Alman. Looking to the next stage of their research, Dr. Alman said that they are "expanding their study of developmental pathways in neoplasia to other musculoskeletal tumors, such as cartilage tumors."

Victor M. Goldberg, MD, vice chairman, grants, OREF, said, "the studies by Dr. Alman will provide molecular basis of new biological treatments for this disabling disease."

The $20,000 OREF Clinical Award, instituted in 1995, recognizes outstanding clinical research related to musculoskeletal disease or injury.

The AAOS administers the program.

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Last modified 22/February/2000 by IS