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Brunhilde Felding

Interfering with the Spread of Breast Cancer and Melanoma

Breast cancer and melanoma have a propensity to metastasize and when they do, they can be deadly.

Metastasis is a dangerous phenomenon in which cancer cells separate from a tumor mass, move through the bloodstream, anchor down in a distant tissue or organ, and begin a new cancer that might compromise the function of that organ. While surgeons can remove cancerous tissue, such procedures are greatly complicated if a tumor spreads to other organs. Although science and medicine have made tremendous strides in early detection and successful treatment, breast cancer and melanoma, the deadliest type of skin cancer, still claim tens of thousands of lives a year - usually the end result of metastasis.

What leads tumor cells to metastasize? What determines where the metastatic cells go? Why do breast cancers typically metastasize and form satellite tumors in the brain, lungs, liver, and bones? What is it about the vascular cells in these tissues that interacts with circulating breast cancer cells and allows them to invade, forming a new tumor?

Scripps Research Associate Professor Brunhilde Felding, Ph.D., who works on metastatic melanoma and breast cancer cells, is working to find answers to these questions.

"Too many patients still die from metastatic breast cancer and melanoma," said Brunhilde. "What we are trying to find out is what determines whether or not breast cancer or melanoma cells will metastasize. Our goal is to develop new therapies that can eliminate the spread of cancer, especially to the brain." Cancer is a complicated disease. It can be caused by subtle mutations within normal cells. After certain mutations occur, a cancer cell grows resistant to normal programmed cell death, dividing out of control, over and over, and forming a solid tumor. Also common to tumor cells are mutations that lead them to metastasize and spread to distant organs. Brunhilde and her group have found a way to inhibit the attachment of disseminating tumor cells and inhibit the metastatic ability of breast cancer cells with special antibodies. She has teamed up with Scripps Research Professor Kim Janda, Ph.D., who has generated a combinatorial antibody library from blood samples from numerous cancer patients, in order to isolate antibodies that are present in the blood of cancer patients and recognize metastatic tumor cells. Brunhilde and her team have found antibodies in the immune repertoire of cancer patients that target the tumor cells.

"Our work has shown that cancer patients can produce antibodies that may very actively interfere with metastasis," said Brunhilde. "We found antibodies that block the ability of human breast cancer cells to metastasize and help extinguish breast cancer that had already spread. Optimizing these antibodies, we might be able to develop powerful anticancer drugs that can inhibit cancer spreading. I think we're moving in the right direction."

This finding is highly significant because of the potential of using such antibodies as a new way to treat cancer. Despite recent progress in cancer therapy, no treatment is known today that prevents cancer spreading.

"One great thing I appreciate here at Scripps Research is that you can have very exciting collaborations merging biology with chemistry, such as this one with Dr. Janda. The work in my lab has really benefited from all of these interactions. In addition to my faculty colleagues, the young researchers who come to Scripps Research for their post doctoral studies are so very, very gifted - it's difficult to find good people like these who work so hard and are driven to fight disease developing their own scientific careers."

"I also find you really have the freedom to explore ideas here," said Brunhilde, who left Scripps Research for a few years and established a research lab in a pharmaceutical company before coming back. "This freedom in research is very important to developing new concepts that can lead to innovative therapies." Brunhilde's laboratory has discovered a molecule critical for the spread of melanoma. In another collaboration with Scripps Research Professor Dale Boger, Ph.D., the team is screening inhibitors against this molecule to find a new treatment for metastatic melanoma.

Brunhilde is also collaborating with Scripps Research Professor Eric Topol, an expert in genomics, in examining the genes of healthy senior citizens and how these genes may have protected them against cancer while others are afflicted. The study involves examining how a good immune system can stop someone from developing cancer with the goal being to "fish out" the best antibodies which might be used as future cancer treatments.

Brunhilde's research on cancer metastasis to the brain is fairly unique among researchers across the country. "It's difficult to conduct experiments on brain metastasis and there are no therapies out there, yet the need is so great - even a little progress could lead to a breakthrough" she said. "We're making progress here though a close collaboration with neurosurgeons at UCSD who have made metastatic brain lesions available for our study."

Brunhilde recently hosted a group of breast cancer advocates from the National Breast Cancer Coalition Fund (NBCCF). NBCCF has spearheaded a major increase in federal funding for breast cancer research. They came to Brunhilde's lab to see her significant research firsthand.

"The visit was a great success," said Brunhilde. "It not only raised the profile of Scripps Research among advocates, but it also gave my lab a big boost in motivation to hear what breast cancer survivors hope to see accomplished in breast cancer research. It brought home why we're doing this research."

Brunhilde came to Scripps Research in 1993 after receiving her Ph.D. from Phillips University in Germany. "It has been a labor of love," she said. "The research has really allowed me to express myself and make a difference."

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"Too many patients still die from metastatic breast cancer and melanoma," says Professor Brunhilde Felding.