Improving Treatment of Deadly Pediatric Brain Tumors

How were you introduced to biomedical research and what did your graduate studies find?

I became interested in conducting biomedical research as a medical student in Austria. Due to a long-standing partnership between my medical school and Mayo Clinic, I had the opportunity to conduct a research project for my medical school thesis under the supervision of neurosurgeon David Daniels, M.D., Ph.D. The experience strengthened my interest in translational research and fueled my desire to pursue a career devoted to understanding and treating neurosurgical diseases as a physician-scientist. After completing my medical degree, I returned to Mayo Clinic to pursue a Ph.D. in Dr. Daniels' laboratory.

My graduate research focused on brain tumors that occur in children. Pediatric high-grade gliomas are uniformly lethal tumors for which no cure has yet been identified. They include a type of tumor known as diffuse midline glioma, or DMG. One significant issue in treating DMGs is the blood-brain barrier that protects the brain from drugs that are administered systemically. A new neurosurgical approach, called convection-enhanced delivery (CED), infuses therapeutics directly into the tumor and is currently being studied as an approach that can provide maximum benefit with minimal systemic toxicity. My dissertation sought to identify the optimal characteristics of drugs that are candidates for CED therapy, to evaluate the potential of drugs that have already been approved by the Food and Drug Administration, and to explore adding innovative immunotherapeutic approaches in the management of these deadly brain tumors.

My studies reviewed and synthesized the current literature on DMGs, encompassing epidemiological and clinical aspects, molecular characteristics, established treatment modalities, and emerging therapeutic investigations. We employed chemical modeling to categorize potential CED small-molecule drugs, based on their innate chemical and biological properties. In a parallel project, we delineated the therapeutic potential of immunotherapy in a subset of high-grade gliomas. We demonstrated that combined radiation therapy plus immunotherapy treatment via convection-enhanced delivery represents a promising therapeutic avenue for DMG. We also introduced a novel method for the development of DMG patient-derived cell lines, which are useful tools for testing new therapies. The work has added to the discussion of contemporary and innovative concepts in the direct delivery of targeted therapeutics to DMG tumors.

What's next?

After successfully defending my Ph.D., I have started my residency training in Neurologic Surgery at Mayo Clinic in Rochester. My career goals are to treat pediatric and adult patients with brain tumors and other neurosurgical diseases and to develop new therapies to improve patient outcomes.