In the fullness of time, small molecule inhibitors of BRAF may be used for the treatment of BRAF mutant pediatric LGAs. However, multiple protein kinases have been shown to be co-activated in high-grade adult gliomas, and this is likely to be the case in BRAF-transformed pediatric astrocytomas as well. Complimentary signaling pathways are both an obstacle and an opportunity for targeted therapy strategies. An RNAi screening core will allow us to conduct a kinome-wide genetic screen for additional druggableÓ” protein kinases that cooperate with BRAF to dysregulate the proliferation of normal neural progenitor cells. In addition RNAi screening complements DNA sequencing as a route to knowledge about other kinds of genes (e.g., GTP-binding proteins, transcription factors) that might underlie these tumors.

Dana Farber Cancer Institute, Dr. Chuck Stiles