Contact: Cindy Starr
A $50,000 Molecular Therapeutics Program Pilot Grant will support a quest to understand and prevent the spread of medulloblastoma, the most common childhood brain cancer. The grant will support the work of Timothy Phoenix, PhD, assistant professor of pharmaceutical sciences at the University of Cincinnati’s James L. Winkle College of Pharmacy.
The grant was announced by David Plas, PhD, associate professor of cancer biology at the UC College of Medicine and holder of the Anna and Harold W. Huffman Endowed Chair in Glioblastoma Experimental Therapeutics at the UC Brain Tumor Center.
The grant will enable Phoenix to pursue research into medulloblastoma’s distinct subgroups, which differ greatly in their tendency to migrate from the brain to the spinal fluid, to the spinal cord and even to areas outside the brain and spine. The tendency to migrate, or metastasize, has been characterized by how closely the tumor cells adhere, or stick together. Those that adhere loosely are most apt to spread throughout the brain and central nervous system.
“When a medulloblastoma brain tumor metastasizes, the outcome is likely to be poor,” Phoenix says. “As such, there is a critical need to understand mechanisms that drive differences in metastatic frequency among the four medulloblastoma subgroups and to develop new biomarkers and therapies that prevent metastasis from occurring.”
Phoenix, who has been studying medulloblastoma subtypes for more than six years, postulates that the potential for medulloblastoma cells to either remain clustered together or to metastasize is determined by specific mutations. The mutations also have been found in medulloblastoma tumors that recur, including those initially at low risk of metastasis.
The high-risk medulloblastoma subgroup is metastatic in 50 to 70 percent of cases, while the low-risk medulloblastoma subgroup is metastatic in about 5 percent of cases.
By studying the medulloblastoma subgroup with the least risk of metastasis and the subgroup with the greatest risk, Phoenix hopes to determine the role that mutations play. He will use an animal model to identify specific genes and signaling pathways that regulate metastatic capabilities.
“Relatively little is known about the mechanisms that promote metastatic dissemination, or why differences exist between molecular subgroups,” Phoenix says. “The development of biomarkers that predict metastasis could provide us with the potential to translate our findings into clinically relevant diagnostic tests and future therapies.”
Medulloblastoma is the most common malignant pediatric brain tumor, representing about 20 percent of all pediatric cancers of the brain and spinal cord. Medulloblastomas occur in the cerebellum, which is located in the back of the brain. The cerebellum plays an important role in motor control, including walking, balance and fine motor coordination.
The four medulloblastoma subgroups are known as WNT, SHH, Group3 and Group4. Treatment is determined by the patient subgroup and the patient’s age.
The Molecular Therapeutics Program exists within the UC Brain Tumor Center, which is part of the UC Gardner Neuroscience Institute and the UC Cancer Institute. The program supports discovery and translational research to advance the care of primary and metastatic brain tumors in children and adults. Metastasis can spread outward from the brain, as with medulloblastoma. More commonly, metastasis reaches the brain from tumors of the lung, breast, kidney or skin (melanoma).
Phoenix’s assistant professorship is supported by both UC and Cincinnati Children’s Hospital Medical Center.