Targeting Cancer Stem Cells to Stop Brain Tumors
Monday, October 30, 2006 - Research on a novel approach to brain cancer – exploring the notion that the source of a brain tumor is a normal stem cell that has gone bad – is moving forward thanks to an award from the James S. McDonnell Foundation to a neurologist at the University of Rochester Medical Center.
Steven Goldman, M.D., Ph.D., professor in the Department of Neurology and chief of its Division of Cell and Gene Therapy, is one of six recipients around the nation to receive a research award from the foundation’s 21st Century Science Initiative in Brain Cancer Research. The award, one of the most prestigious in the realm of brain cancer research, funds for the next four years Goldman’s efforts to look for new ways to understand and treat brain tumors, which affect about 17,000 people in the United States each year. The award is part of approximately $1 million in private foundation support that Goldman has received recently to continue his stem cell research; those funds are in addition to several ongoing projects funded by the National Institutes of Health.
Goldman’s brain tumor research focuses on the raw power that stem cells wield in the human body, for good and for bad. The cells can be very rare in the brain, sometimes literally just one in 10 million cells. But they are critical to the brain’s ability to recover from brain injury, acting as master cells, providing a source of new cells, and retaining the ability to become nearly any type of brain cell. But when a stem cell goes bad, scientists like Goldman are discovering that the result can be a brain tumor. Stem cells gone awry are hundreds of thousands of times more plentiful in a typical tumor than stem cells should be, helping to make brain tumors especially resistant to chemotherapy.
Goldman, a neurologist who frequently treats patients with brain tumors, is using his expertise with stem cells to explore new ways to fight the disease.
“Overall the treatments for brain cancer aren’t much better than they were decades ago,” said Goldman. “Surgery is a bit better, and our ability to target the tumor with radiation is much better, but the survival rate has not improved much, and chemotherapy generally does not work well. Most patients today have the same prognosis that patients did years ago. Obviously, we need to do something different.”
Goldman is internationally recognized for his contributions to the development of stem cell therapy. In particular, he has created a set of techniques for pinpointing key cells of interest in brain tissue, then isolating them to direct their development. Like a person growing into adulthood, a stem cell has many options for what to “become,” what role to play in the body. In the brain, it might become a cell that creates electrical signals crucial to movement, or it might become a support cell that makes insulation for nerves.
Goldman is sorting out the cues within the brain that determine what a stem cell ultimately does. He is finding that the assortment of brain chemicals, proteins, nutrients, and other signals – the “biochemical brew” of exactly where a stem cell is located in the brain – is crucial in determining what that cell becomes.
In the work recognized by the McDonnell Foundation, Goldman is isolating stem cells in various stages of development, and then analyzing the differences in the signals that are on or off. He compares stem cells involved in the formation of brain tumors to their healthy counterparts, attempting to identify exactly which genes and proteins play a role in turning a healthy stem cell into the creator of a cancerous tumor.
Using this method, a member of Goldman’s team, Fraser Sim, Ph.D., has identified a molecule that appears to cause a rare type of brain tumor known as a neurocytoma. Goldman hopes to use the same approach to ferret out the causes of other types of brain tumors, and even other types of cancer. Currently he is collaborating with researchers from Harvard, the University of California at San Francisco, and the University of California at Los Angeles to look for the genes that play a role in causing a variety of brain and other cancers.
Goldman also recently received significant support from the Miriam and Sheldon Adelson Program in Neural Repair and Rehabilitation for related work. He is studying many of the same genes involved in brain tumors, but he is looking at the normal function they have in the healthy brain. He is also using the same techniques to study another set of cells derived from stem cells, motor neurons, which are affected in diseases like Huntington’s disease, spinal cord injury, and amyotrophic lateral sclerosis, or Lou Gehrig’s disease.
In addition to its impact on patients with brain tumors, ALS, Huntington’s disease and spinal cord injuries, Goldman’s research is directed at a variety of neurological diseases that may benefit from stem cell therapy. These include Parkinson’s disease, multiple sclerosis, and several rare but fatal forms of childhood neurodegenerative disease. In many of these diseases, it’s the demise of just one particular type of cell in one location that causes most of the symptoms. More than 30 people in his laboratory are focused on developing stem-cell therapy to treat these diseases, thanks to funding from these foundations as well as several other foundations, corporate sponsors, and government agencies.
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- Tom Rickey
- University of Rochester Medical Center
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