Kinome profiling of WT and Nf2 KO human Schwann cell lines

Patients with neurofibromatosis type 2-related schwannomatosis (NF2-SWN) develop hallmark tumors on their vestibular nerves, leading to hearing loss and numerous associated morbidities. Currently, there are no targeted therapeutic options for treating these tumors. In prior work, our group had identified brigatinib as a potentially active drug in the treatment of murine models of NF2-SWN and meningioma, leading to a clinical trial in NF2-SWN patients testing brigatinib. Kinome profiling revealed that brigatinib resulted in the inhibition of focal adhesion kinase 1 (FAK1, encoded by the PTK2 gene). To test the contribution of FAK1, we generated a genetically engineered mouse model of NF2-SWN with Fak1/Ptk2 deletion in tumorigenic cells of origin. Genetic ablation of Fak1/Ptk2 preserved hearing in the mice and reduced tumorigenesis. Here we used an immortalized human Schwann cell line, 02.3 2lambda, Control and 3 NF2 KO clones, to perform kinome profiling.