Targeting the MAPK signaling pathway to improve survival in AT/RT
Mentor Name: Jeffrey Rubens
Atypical teratoid/rhabdoid tumors (AT/RT) are deadly tumors mainly affecting infants between the age of 0-3. Overall survival is 37% and for patients with relapsed disease there is no known cure. The Pacific Pediatric Neuro-Oncology Consortium (PNOC) aims to open a multi-arm clinical trial testing novel therapies for patients with relapsed AT/RT. We aim to develop the pre-clinical justification to add new therapies to arms of this clinical trial. We have previously demonstrated that AT/RT are dependent on the MAPK signaling pathway to drive their aggressive growth and survival. Mirdametinib is a highly brain penetrant inhibitor of the MAPK pathway which has extensive safety data in other pediatric clinical trials. In this project we develop mouse models of AT/RT and treat with Mirdrametinib to understand the impact of inhibiting the MAPK signaling pathway on survival. The results of these studies will rapidly translate into a new clinical trial for patients with relapsed AT/RT.
