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Guidelines for sites linking to mayoclinic.orgAs a young graduate student studying endocrinology, John A. Copland, Ph.D., realized quickly that scientific knowledge alone wouldn't fulfill him. Studying the hormones that influence animal reproduction — a major component of his graduate studies early on — can sometimes foster such revelations. "I thought to myself, I don't know if I can do this for the rest of my life," recalls Dr. Copland, now a molecular biologist at Mayo Clinic Cancer Center in Jacksonville. "I wanted to make an impact on human disease."
Dr. Copland is applying that interest to renal cell carcinoma (RCC), the most common form of kidney cancer in the United States, which currently results in about 36,000 new cases each year and about 13,000 deaths annually, according to the American Cancer Society.
Adding weight to those figures are statistics showing that RCC is difficult to treat. Five-year survival rates for patients diagnosed when the cancer is confined to the kidney are between 60 percent and 75 percent, but once it spreads beyond the kidney, five-year survival rates drop below 15 percent.
Dr. Copland believes he can help change those statistics by coupling genomics technology with his background in molecular biology. Using a technique known as genomic profiling, he is comparing tissue from RCC tumors with samples of normal kidney tissue from the same patient to identify genes that are, in essence, overactive or underactive in RCC.
This approach uses gene microarrays or "gene chips," small devices that easily fit in the palm of a hand and quickly measure the activity of each gene in the human genome in a given piece of tissue. In Dr. Copland's studies to date, those chips have shown that thousands of genes may have a connection to RCC.
That's where molecular biology comes into play. All those genes can be grouped by their functions in cells, which then make it possible to identify "master genes." These master genes control signal pathways that affect the behaviors of hundreds of genes and initiate the changes that make normal cells cancerous, Dr. Copland says. That is the key to better therapies.
"I think we can go from a 1,000 or 3,000 candidate genes to anywhere from five to 30 master genes and develop combination therapies that hit those targets," Dr. Copland says. "With that approach, we can halt the disease."
To date, Dr. Copland has identified one promising master switch for RCC, a gene called TGF beta, which influences the proliferation and spread of RCC cells. The task now is to further validate his findings about TGF beta and to discover other master switches. "We have all of the tools, and that's what's exciting," Dr. Copland says. "Five years ago, we didn't have the same ability to quickly make discoveries that would change the practice of medicine."
The state of Florida has taken note of the health risk that renal cell carcinoma (RCC) represents, as well as Mayo Clinic Jacksonville's potential for dealing with that concern. John A. Copland, Ph.D., is part of a four investigator group that has received a $1 million grant from a "Big Tobacco" lawsuit fund that Florida established to support research related to cigarette smoking.
The grant is the largest award possible under the fund, and with it Mayo is launching a project to further examine the connection between RCC and cigarette smoking. The investigators say the initial funding will help them attract long-term support from the National Institutes of Health or a similar organization. With the state funding, they will be able to collect data showing that their research has potential, which better positions Mayo for funding from the government and other major granting agencies. And, in studying a common risk factor for the disease — cigarette smoking — they will learn about basic mechanisms and therapies that will help improve diagnoses and treatments for all RCC patients.
The program's parts are:
The group's strength, Dr. Parker says, is its ability to investigate issues across the entire spectrum of RCC. "It's the classic story of Mayo's strength in research," he says. "We have the ability to collaborate across many disciplines, and that means we can investigate a range of topics in RCC, from basic mechanisms all the way to patient care and even further into issues of quality of life. It's one of th biggest reasons we received the $1 million grant."
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