CDC42 RHOJ Interaction Inhibitors for the Treatment of Neurofibromatosis

Neurofibromatosis type 2, a disorder driven by Merlin mutation, can cause significant life long issues such as permanent hearing loss. While recent advances have identified the drug selumetinib as a promising therapy for these tumors, this drug can induce serious side effects that reduce compliance and tolerance. This is a particular problem as NF2 patients will require prolonged treatment with these agents to preserve their hearing. To combat this issue, researchers are looking for compounds that can be used in conjunction with selumetinib in an effort to increase the effectiveness of overall treatment. Researchers have developed a lead molecule, ALY101, that inhibits angiogenesis, or the formation of new blood vessels that support tumor growth. The compound has drug-like properties, is well tolerated in experimental animals, and can inhibit the growth of tumor grafts in mice. This project proposes to examine whether this compound could be a new treatment for NF2 by examining whether it can inhibit the growth of patient-derived cell lines in a laboratory before developing a clinical trial. Rare and high quality cell lines provided by the Pediatric Brain Tumor Atlas will support this project. Completion of this work will lead to future studies investigating whether this drug could be used to treat NF2 patients.