CINCINNATI—A small pilot cancer study funded by Walk Ahead for a Brain Tumor Cure has led to a $1.67 million, five-year grant from the National Institutes of Health (NIH) that will enable University of Cincinnati (UC) researchers to study a novel strategy to combat glioblastoma multiforme.
Atsuo Sasaki, PhD, a member of the Brain Tumor Center at the UC Neuroscience Institute and UC Cancer Institute and the study’s principal investigator, will use the funds to test his novel hypothesis that glioblastoma, the highly aggressive brain cancer, can be inhibited by targeting PI5P4Kβ, a key player in cancer that has recently emerged.
"Glioblastoma multiforme (GBM) is the most prominent and malignant primary brain tumor, and it tends to be stubbornly resistant to conventional therapies,” notes Sasaki, assistant professor in the division of hematology oncology at UC and a member of the Cincinnati Cancer Center. "There is a critical need for new therapeutic modalities and agents that improve patient outcome.”
Glioblastoma, which strikes an estimated 17,000 Americans each year, defies conventional treatments such as surgery, chemotherapy and radiation therapy, in part because it is a diffuse tumor that cannot be removed or targeted easily. The cancer also confounds doctors because glioblastoma cells have proven to be such stubborn survivalists.
With funds from Walk Ahead and other sources, Sasaki and his laboratory team have become the first known researchers to go after the "boiler room” of energy-guzzling glioblastoma cells. They hypothesize that they can stop the growth of glioblastoma cells by interfering with the PI5P4Kβ (phosphatidylinositol-5-phosphate 4-kinase-β) pathway. With the infusion of federal dollars, Sasaki will use both pharmacological and molecular approaches that target PI5P4Kβ in a cell culture and in animal tumor models.
Specifically, their research focuses on phosphoinositide signaling. Phosphoinositide is a cellular messenger that plays a role in controlling cellular activities such as growth and proliferation. Once cells have lost control of phosphoinositide signaling, the risk for disease, particularly cancer, increases. Conversely, when the signaling pathway is disrupted, Sasaki says, "we expect to see a decrease in tumor growth.”
Finding a way to combat glioblastoma cells without harming normal cells would bring an important new therapy to the treatment of the aggressive cancer, Sasaki says. "The results of this research may also have a direct impact on treating brain metastases secondary to lung cancer, breast cancer, and melanoma.”
The NIH grant is categorized as an R01, a highly competitive award that in 2013 was distributed to only 17.5 percent of all applicants. The award represents a milestone for Sasaki, a young researcher who came to UC from Harvard University in 2012. It is also the first million-dollar grant to be seeded by the five-year-old Walk Ahead for a Brain Tumor Cure, which has raised more than $850,000 for education and research.
"We are thrilled by the awarding of a prestigious R01 grant to Sasaki,” says Ronald Warnick, MD, medical director of the UC Brain Tumor Center and the John M. Tew, Jr., MD, Chair in Neurosurgical Oncology. "The award represents a significant career accomplishment for Dr. Sasaki and national recognition for the UC Brain Tumor Center.
"It also marks a milestone for members of the UC Brain Tumor Center’s Community Advisory Council and for all of the donors who have supported our center. In a very concrete way, we have shown that community involvement can make a difference in scientific discovery and in the future health of our citizens.”
The pilot study was funded by a UC Brain Tumor Center pilot grant ($100,000 over two years), which was fueled by Walk Ahead for a Brain Tumor Cure. Funding also came from the American Association of Neurological Surgeons (AANS) Section on Tumors/BrainLab International Research Fellowship, which supports Sasaki’s lab member, Kazutaka Sumita, MD, PhD, a postdoctoral fellow in the division of hematology oncology.
The 2014 Walk Ahead event will take place Oct. 26 at Sawyer Point. For more information, visit http://www.walkahead.org.