Research And Grants

Identifying Novel Treatment Combinations Targeting ERK Signaling Dependence in Pediatric Glioma

High-grade gliomas (HGG) are aggressive brain tumors that are a leading cause of cancer death in children and young adults. Some HGGs have specific changes in their DNA (like BRAF or NF1 mutations) that affect a pathway called RAS-ERK, which controls how cells grow and repair damage. While drugs that target this pathway (e.g., MEK inhibitors) can help, they don’t cure the cancer, and cancers often find ways to resist treatment.

Our research uses a different approach: combining MEK inhibitors with other treatments that damage the cancer cells' DNA. We discovered that when the RAS-ERK pathway is blocked, the tumor cells become worse at repairing DNA. This weakness makes them more vulnerable to treatments like chemotherapy or radiation. We are testing these combinations in lab-grown tumor cells and in mice with human brain tumors. Our goal is to find out which drug combinations work best and are safe enough to eventually try in children with HGG or similar tumors.

By learning how to use these weaknesses in cancer cells, we hope to create better, more effective treatments for young patients who currently have very few options.