EXTH-39. BIOMARKER DRIVEN TARGETING OF RECURRENT IDH MUTANT GLIOMA WITH ABEMACICLIB

Abstract Despite initial responsiveness to standard treatments like radiation and chemotherapy, IDH mutant gliomas inevitably recur, become more clinically aggressive, lead untimely death. The aggressive change in clinical outcome is driven by insensitivity conventional methods of treatment, necessitating an improved therapeutic strategy at this stage the disease. Greater than 20% recurrent exhibit homozygous loss CDKN2A, leading endogenous CDK4/6 inhibitor p16 aberrant signaling through CDK-RB pathway. We hypothesized that CDKN2A leads enhanced sensitivity inhibitors which have been approved for use a variety other cancer types. examined panel patient-derived with either or CRISPR-mediated gene deletion treatment inhibitors. observed correlation between cytotoxicity following abemaciclib these glioma models. characterized cell cycle profile flow cytometry western blotting both sensitive resistant lines. Further, resulted significant slowing tumor growth rate subcutaneous model. Survival studies intracranial model are ongoing. These preclinical results provide foundational data support biomarker-driven trial patients glioma.