June 22, 1999 (Toronto, June 21, 1999) - The cellular fuel which powers the growth of Hodgkin's disease has been identified for the first time by a research team at Princess Margaret Hospital's Ontario Cancer Institute, the University of Toronto and the Amgen Research Institute. The research team also discovered that the fuel is actually manufactured by the tumour cells themselves.
The finding paves the way for future research into targeted ways to stop the growth of Hodgkin's disease tumours with little or no side effects, and is the cover article in the June 21, 1999 edition of the Journal of Experimental Medicine.
"Huge Clinical Potential"
"I'm particularly excited because for the first time we have identified the engine that drives at least some Hodgkin's cancer cells to multiply. We are now working to find a way to shut down that engine. These findings have huge clinical potential," said Dr. Tak W. Mak, senior scientist at the Ontario Cancer Institute, director of the Amgen Research Institute and professor of Medical Biophysics and Immunology at the University of Toronto.
Researchers discovered that a growth factor, called Interleukin-13 (IL-13), is secreted by Reed-Sternberg cells, the cancer cells of Hodgkin's disease. IL-13 then fuels the growth of more Reed-Sternberg cells in a cyclical process of self-proliferation.
Using gene chip technology, lead author Dr. Ursula Kapp, a scientist at the Amgen Institute at the time of the study and now a member of the departments of hematology and oncology at University Medical Centre in Freiburg, Germany, examined 950 tumour genes in order to identify which ones are specifically expressed in Hodgkin's disease cells. She found that IL-13 is consistently over-expressed in Hodgkin's disease. Her colleague, Dr. Bruce Patterson, a pathologist at Princess Margaret Hospital and co-author of the study, determined that it was the Reed-Sternberg cells themselves that produce the deadly growth factor.
"Now that we know IL-13 plays a major role in the growth of at least some Hodgkin's tumours, we can begin to look at new treatments for the disease using IL-13 neutralizing antibodies or by blocking IL-13 production altogether within Reed-Sternberg cells," said Dr. Kapp. "We are particularly excited to have shed new light on this rare, but serious form of cancer."
Killer Side Effects
Hodgkin's disease, a malignancy of the body's immune system, most commonly strikes young adults in their twenties and thirties, first appearing as enlarged lymph nodes in the neck or chest. Most Hodgkin's patients are treated with radiation therapy, chemotherapy or a combination of the two. However, a significant number of patients develop infertility, heart disease or another form of cancer as a result of treatment within five to fifteen years after being diagnosed with Hodgkin's disease.
Although Hodgkin's disease has nearly an 80 percent cure rate, Dr. Patterson cautions that the high cure rate can come at a high price. "We have reached the point where the risk of complications from treatment for Hodgkin's disease is now becoming significant," said Dr. Patterson. "With present treatments, some patients are dying from the complications of treatment rather than from the disease itself."
Researchers hope that the discovery of IL-13's role in Hodgkin's tumour progression will help them to develop targeted treatments for the disease that cause few, if any, side effects. Rather than subjecting Hodgkin's patients to potentially harmful chemicals or radiation, researchers hope to find a way to stop the growth of Hodgkin's disease cells before the disease progresses.
Dr. Mak's team found that blocking the effects of IL-13 resulted in the Reed-Sternberg cells' inability to multiply. "We determined that if IL-13 was making these cells divide and grow, we simply had to deprive them of IL-13 and they should stop dividing," said Dr. Mak. "It worked. In about eighty hours Reed-Sternberg cells in a test tube almost completely stopped growing. This discovery gives us great hope that we will someday find a rational way to target and kill Reed-Sternberg cells without subjecting patients to serious side effects. That is the role of future cancer researchers - to develop rational approaches to treating cancer with minimal side effects and maximum quality of life. Discoveries like this one will help us to do that."
Princess Margaret Hospital, a teaching hospital of the University of Toronto, has achieved an international reputation as a global leader in the fight against cancer and is considered to be one of the top comprehensive cancer research and treatment centres in the world. The Ontario Cancer Institute is the Research Institute of Princess Margaret Hospital which, along with the Toronto General Hospital and the Toronto Western Hospital, is a member of the University Health Network.
The AMGEN Research Institute is an integral part of AMGEN, the world's largest biotechnology company and an innovative and pioneering world-wide organization dedicated to the research and development, manufacture and marketing of cost-effective human therapeutics using recombinant DNA technology.
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