Glioblastoma multiforme (GBM) remains one of the most challenging forms of malignant brain tumors. This fast-growing central nervous system tumor forms in the supportive tissue of the brain and spinal cord and results in a median patient survival of just 15 months.
Bahassi is using whole genome sequencing to identify and then track specific tumor mutations (circulating mutant DNA) through the blood.
Whole genome sequencing is a laboratory process to determine the complete DNA sequence of a person’s genome (i.e., complete hereditary makeup)—at a single time. Genetic instructions from DNA fuel all biologic developments and functions in the body.
"Tumors release small fragments of DNA that carry the same genetic information we would get by doing a tissue biopsy in the brain. Gathering this information from the patient through blood samples—before, during and after treatment—could tell us whether the patient is responding to treatment or likely to have a relapse through blood samples and avoid multiple, invasive brain tumor biopsies,” says Bahassi, who is also a research assistant professor in the UC College of Medicine Department of Internal Medicine, Division of Hematology Oncology.
"Utilizing whole genome sequencing could help identify changes in the genomes of brain tumors that drive cancer progression and aid in the development of noninvasive biomarkers to help follow treatment effectiveness and predict tumor recurrence,” adds Bahassi.
A non-invasive test allowing for personalized therapy, says Ronald Warnick, MD, a Mayfield Clinic neurosurgeon and medical director of the UC Brain Tumor Center, would be the "Holy Grail” in the brain tumor field.
"Currently, the best we can offer patients is standard therapy—surgery, radiation and chemotherapy—but the information gleaned from the type of biomarker test we are researching would allow us to tailor a patient’s treatment to account for the specific genetic defects within the tumor,” adds Warnick.
Treating GBM is tricky: the tumor typically infiltrates the brain, so removing all of the tumor is virtually impossible; brain tumor cells can be resistant to radiation; and chemotherapy regimens are often ineffective at breaking through the blood-brain barrier without toxic effects to the patient.
"We monitor for signs of recurrence using standard magnetic resonance imaging (MRI). A non-invasive blood test could allow us to detect tumor recurrence before we see any signs of recurrence on the MRI. It can also help differentiate between tumor regrowth and treatment effects (i.e. scar tissue)—which can look remarkably similar on an MRI. All of this together would enable us to make a very specific prognosis and give our patients the best changes for survival,” says Warnick.
Basic Scientists and Clinicians Working Together
At the UC Brain Tumor Center, basic scientists and neurosurgeons are working together to tackle the problem in a pre-clinical study using human brain tumor tissue samples. The original study included 10 tumor samples and was funded by UC and small foundation grants from the Mayfield Education & Research Foundation, Shemenski Foundation and LCS/Sahlfeld Foundation
Additional funding from the CTSA has given Bahassi and Warnick resources to collect whole genome sequencing data on an additional 40 patients from the UC Brain Tumor Center to determine if the approach is feasible for a phase-1 clinical trial.
The UC Brain Tumor Center is one of nine centers of the UC Neuroscience Institute and one of five comprehensive disease-based centers of the UC Cancer Institute. Both institutes are partnerships of UC Health and the UC College of Medicine. Learn more about the UC Brain Tumor Center at ucbraintumorcenter.com.