UCLA

There is an increasing recognition of the important role cancer predisposition syndromes play in the development of oncological diseases. Consequently, there's an urgent need to identify and understand these syndromes to uncover underlying disease mechanisms. Among these syndromes are Rhabdoid Tumor Predisposition Syndrome Type 1 (RTPS-1) and Neurofibromatosis Type 1 (NF1). RTPS-1 is marked by mutations in the SMARCB1 gene, whereas NF1 is linked to mutations in the NF1 gene. Given their rarity, there's a critical need for novel therapeutic approaches and preclinical models to accelerate the translational research pipeline. Previously, our team developed genetically engineered animal models (GEMM) for both RTPS-1 and NF1. This dissertation aimed to explore the mechanisms of rhabdoid tumorigenesis by pinpointing specific biomarkers and drug targets within the RTPS-1 GEMM. Additionally, we endeavored to establish a large animal porcine model for RTPS-1 as a proof-of- concept. We then investigated Cold Atmospheric Plasma (CAP) as a novel therapeutic strategy to target NF1-associated peripheral nerve sheath tumors. Our results showcased the ability of CAP to impact cellular oxidative stress, paving the way for its potential application in treating tumors associated with cancer predisposition syndromes.