Novel Therapeutic Target for KIAA1549-BRAF-Rearranged Pediatric Gliomas

Award: $750,000 over 2 years (awarded 2024)
Principal Investigators: Pratiti (Mimi) Bandopadhayay, MBBS PhD, and Rameen Beroukhim, MD PhD, Dana-Farber Cancer Institute
Funding Partners: Catching Up With Jack; Hope for Kids Fund; Jacks Drive 55 Foundation through PBTF’s PLGA Fund

Pediatric low-grade gliomas (pLGGs) are the most common group of pediatric brain tumors and associated with significant morbidities. The most frequent driver alteration in pLGGs is KIAA1549-BRAF rearrangements. While MAPK pathway inhibitors have shown promise in targeting BRAF activation, they are not curative and many pediatric low-grade gliomas have primary resistance to these inhibitors.

Through previous research funding, Drs. Pratiti (Mimi) Bandopadhayay’s and Rameen Beroukhim’s research team at Dana-Farber Cancer Institute have identified a specific protein complex that is highly and specifically dependent on cells expressing KIAA1549-BRAF, with the potential to be a therapeutic target for KIAA1549-BRAF-rearranged pediatric gliomas.

With this grant’s new funding, the team plans to test the protein complex’s impact on this type of tumor and investigate the combined treatment of MAPK inhibitors and complex suppression to determine if it results in sustained responses in pediatric glioma models.