Recent study pinpoints the genetic cause of glioblastoma - the most common and aggressive form of primary brain cancer. The study also found that drugs that target the protein produced by this genetic aberration can dramatically slow the growth of glioblastomas in mice. The findings were published today in the online edition of the journal Science.
"Our findings are doubly important," said study leader Antonio Iavarone, MD, professor of pathology and neurology at CUMC, and a member of the Herbert Irving Comprehensive Cancer Center (HICCC) at NewYork-Presbyterian Hospital/Columbia University Medical Center. "From a clinical perspective, we have identified a druggable target for a brain cancer with a particularly dismal outcome. From a basic research perspective, we have found the first example of a tumor-initiating mutation that directly affects how cells divide, causing chromosomal instability. This discovery has implications for the understanding of glioblastoma as well as others types of solid tumors."
AdvertisementThe fusion of these two genes was observed in just three percent of tumors studied, so any therapy based on this particular genetic aberration would apply to only a small subset of glioblastoma patients. "It's unlikely that we will find a gene fusion responsible for most glioblastomas. But we may be able to discover a number of other gene fusions, each accounting for a small percentage of tumors, and each with its own specific therapy," said co-senior author Anna Lasorella, MD, associate professor of pathology and pediatrics at CUMC and a member of the Columbia Stem Cell Initiative and the HICCC.
"This is a very exciting advance in our understanding of cancer, and perhaps a first step toward a personalized, precision approach to the treatment of glioblastoma," said Stephen G. Emerson, MD, PhD, director of the HICCC and the Clyde '56 and Helen Wu Professorship in Immunology at the Columbia University College of Physicians and Surgeons.
Glioblastomas are tumors that arise from astrocytes, star-shaped cells that make up the brain's supportive tissue. Since astrocytes reproduce quickly and are supported by a large network of blood vessels, glioblastomas are usually highly malignant. It is estimated that these tumors affect about 10,000 people in the United States each year. Glioblastoma is typically treated with surgery, followed by radiation and chemotherapy. However, the disease is invariably fatal, with a median survival of about 14 months after diagnosis, even with aggressive therapy. Glioblastomas took the lives of Senator Edward Kennedy in 2009 and New York Mets all-star catcher Gary Carter in 2012.
Several common single-gene alterations have been observed in glioblastoma. "However, therapies targeting these alterations have not improved clinical outcomes, most likely because they have systematically failed to eradicate the proteins to which the tumor is 'addicted,'" said Dr. Iavarone.
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