Evaluating Therapeutic Vulnerabilities in DIPG Tumors Using High-Throughput Screening
Diffuse intrinsic pontine gliomas (DIPGs) are among the most lethal cancerous tumors known with no effective cure. In an effort to identify drugs for rapid clinical translation, Dr. Daniels' research team performed a rigorous high-throughput in vitro drug screen of Food and Drug Administration-approved chemotherapeutics and epigenetic regulators.
As a result, several major classes of drugs that potently reduce cell viability of DIPG tumors with the H3K27M mutation were identified. These results led the Experimental Drug and Therapeutics for Pediatric Brain Tumor Lab research team to discover a major signaling pathway that has not been previously reported as a therapeutic target for DIPGs. Dr. Daniels' team found proteins in this pathway that were overexpressed in H3K27M tumors compared with Wilms tumors (WT). Furthermore, depletion or inhibition of this pathway selectively inhibits the proliferation of H3K27M mutant DIPG cells, decreases cell colony formation, increases apoptosis compared with WT expressing tumors and restores H3K27 trimethylation patterns.
These studies pave the way for developing molecularly targeted therapies as the understanding of how these mutations lead to tumorigenesis unfolds.