Madeline Miclea
Pronouns: she/her
Research Mentor(s): Kallen Schwark
Research Mentor School/College/Department: Koschmann Lab / Medicine
Program: CG
Session: Session 4 (1:40pm – 2:30pm)
Authors: Madeline Miclea, Madeline Miclea, Kallen Schwark
Abstract
My project aims to characterize the performance of the drug avapritinib as a targeted therapy for pediatric high-grade glioma (pHGG). Advancing research in neuro-oncology is urgently needed as only 10% of patients with high-grade gliomas survive past 2 years. With no effective treatments, the field has turned to targeted therapy as a potential avenue for improving patient outcomes. One of the most commonly altered genes in pHGG is PDGFRA, a tyrosine kinase receptor that is amplified or mutated in roughly one-fifth of pHGG cases. Avapritinib is a new inhibitor that has been shown to target PDGFRA effectively, have few off-target effects, and cross the blood-brain barrier. However, its effectiveness has not been well documented in pre-clinical models with different PDGFRA variants. Our hypothesis is that avapritinib targets mutant PDGFRA more effectively than other inhibitors due to its design against the mutant protein and its high brain penetration, and will target amplified PDGFRA with similar potency but higher specificity.
