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Cohen, along with Viktor Hamburger, Ph.D., of Washington University, and Italian scientist Rita Levi-Montalcini, Ph.D., was investigating nerve growth in chick embryos in the early 1960s. They injected the embryos with an extract from snake venom, thinking that it would stop nerve growth. Instead they were amazed to see an array of new nerve fibers. Eventually, Cohen tried injecting related extracts into baby mice. Not only did the nerves grow, Cohen noticed something equally remarkable. The baby mice opened their eyes several days earlier than normal. The extract was making skin cells grow faster, allowing the eyes to open early. The same thing happened with human skin cells.
Cohen realized immediately that he had stumbled on something revolutionary. “There are very few ways you can improve on nature and make it go faster,” he explained. Eventually Cohen isolated a protein that made the baby mice open their eyes early. It was named epidermal growth factor or EGF because it makes the epidermis or top layer of skin grow.
What started as an interesting theoretical exercise resulted in Cohen’s “aha” moment, and it launched decades of research by cancer scientists who realized that EGF plays a role in cell growth, including cancer cells. Since cancer is the result of uncontrolled cell growth,
finding a way to block that growth is key to treating the disease.
By the 1980s other scientists investigating brain tumors in rats found that a nearly identical cancer-causing gene (oncogene) existed in humans and was present in excessive amounts in about 20 percent of breast cancers. The product of that gene was a receptor that was firing signals for cancer cell growth. Once found, investigators finally had a target for breast cancer – the HER2 receptor. They immediately focused on developing a drug that could block the HER2 receptor. Herceptin is that drug and it is saving the lives of some women whose breast cancer is positive for the HER2 receptor.
Teresa Lundberg was one of the patients enrolled in one of the clinical trials that proved Herceptin could make a difference. “I felt it was another avenue out there to help my chances,” she said. “I didn’t want to sit back and feel that I had not done everything I could to go after this cancer.”
Halfway through that trial, researchers determined Herceptin was showing such strong results it became part of the standard
treatment regimen for every woman in the trial. Today, oncologists routinely test breast cancer patients to find out if their tumor is
positive for the HER2 receptor. The test not only identifies women who should benefit from the drug, it prevents women who are
negative for the HER2 receptor from being exposed to a therapy
that is unlikely to work.
“We wouldn’t have these treatments if somebody hadn’t been working in the lab,” said Lynn Matrisian, Ph.D., professor and chair of the Department of Cancer Biology. “I don’t know if people understand how much time, thought and effort, and trial and error, go into figuring out which discoveries are going to be translated.”
‘We are less in the dark this way’
While serendipity will always play a role in biomedical discovery, translational research is a deliberate approach to transform scientific discoveries from the laboratory into clinical applications for patients – and to take information from the clinic or patient bedside back to the laboratory for exploration.
“Translational research is mechanism-based research that is applicable to patient care,” explained Carlos L. Arteaga, M.D., professor of Medicine and Cancer Biology, and director of Vanderbilt-Ingram’s Breast Cancer Specialized Programs of Research Excellence (SPORE) grant funded by the National Cancer Institute. “We now have biomarkers or targets that we are identifying in tumors, and we have developed drugs to hit those targets. Since we know what the drug hits and we know how it works, we are in a position to understand why it doesn’t work in some cases. We are less in the dark when we do things that way and can provide more information so patients and their doctors can make a more informed decision.”
This search for biomarkers identified in the laboratory produced another new drug, Gleevec, which is showing significant results in many patients with chronic myeloid leukemia. This blood disease occurs when pieces of two chromosomes break off and swap places on the opposite chromosome. This chromosome mix-up causes a blood cell protein to be turned on all of the time, telling the bone marrow to make too many abnormal white blood cells. Gleevec blocks that signal.
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