Pediatric low-grade gliomas with CRAF fusions respond differentially to targeted therapeutics based on their dimerization profiles

American Association for Cancer Research

July 1, 2016
Payal Jain, Tamara Fierst, Amanda Silva, Jake Budlow, Harry Han, Phillip B. Storm, Angela Waanders, and Adam Resnick


Recent studies have identified QKI-RAF1 and SRGAP3-RAF1 as CRAF (or RAF1) fusions in pediatric low-grade gliomas (PLGGs). CRAF fusions, like BRAF fusions are activating mutations driving the mitogen activated protein kinase (MAPK) pathway. Our previous findings suggest effective inhibition of BRAF fusion driven tumors using second-generation RAF inhibitor, PLX8394 and downstream MEK inhibitors (MEKi). We sought to investigate the mechanistic basis of response of CRAF fusions to clinically relevant RAF inhibitors and downstream pathway inhibitors, studying effect on CRAF dimerization profiles.