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AACR-PLGA Fund at the Pediatric Brain Tumor Foundation Research Grant to Optimize Drug Dosing Strategies for Pediatric LGA/LGG Patients

The AACR-PLGA Fund at the Pediatric Brain Tumor Foundation Research Grant to Optimize Drug Dosing Strategies for Pediatric LGA/LGG Patients represents a joint effort to promote and support innovative and collaborative research focused on the most common forms of pediatric brain cancer – low grade glioma/astrocytoma.

2020 Grantee

Karisa C. Schreck, MD, PhD

Karisa C. Schreck, MD, PhD

Assistant Professor
The Johns Hopkins University School of Medicine
Baltimore, Maryland
Functional engagement and effect of RAF-targeted therapies in glioma

Research
Genomic characterization has revealed that pediatric low-grade astrocytoma (PLGA) shares some molecular drivers with pediatric and adult high-grade glioma, specifically activating BRAF-fusion or point mutations. Utilization of RAF and MEK inhibitors (RAFi/MEKi) against these oncogenes is promising in PLGA, but very little is known about bloodbrain barrier penetration, target inhibition in brain, combination with other modalities, or biomarkers of response. Dr. Karisa Schreck and collaborator, Dr. Jean Mulcahy Levy, propose to determine RAFi/MEKi penetration and target engagement in non-enhancing and enhancing brain tumor tissue from children and adults with glioma by leveraging biospecimens from ongoing clinical trials. Biospecimens will be used to determine intra-tumoral drug concentrations, functional ERK inhibition, and correlation with response to treatment. The investigators will also identify a kinome signature for treatment sensitivity using pre-/post- treatment specimens and serial blood samples. These data will help inform future trial design and drug dosing in patients with PLGA.

Biography
Dr. Schreck is an assistant professor of neurology and oncology at the Johns Hopkins University School of Medicine. She received her BS from the New Jersey Institute of Technology, where she majored in biomedical engineering and played varsity soccer. She went on to obtain her MD/PhD from Johns Hopkins University with a focus on the role of neural developmental pathways in glioblastoma. She completed residency in neurology at Johns Hopkins University followed by a fellowship in the joint NIH-Hopkins neuro-oncology fellowship program. The focus of her research is the use of RAF-targeted therapy in brain tumors and mechanisms of resistance.

Acknowledgment of Support
I am appreciative of the Pediatric Brain Tumor Foundation and AACR’s partnership to support my research. This award provides funding to study BRAF inhibitor entry and function in gliomas using clinical trial specimens from patients. This will enable us to design smarter clinical trials and novel drugs against glioma.