2022 LCRF Minority Career Development Award (CDA) in Lung Cancer
Amanda  Bradley, PhD
Fred Hutchinson Cancer Center
Discovering genetic factors of MET Exon skipping and drug resistance in lung cancer
In lung adenocarcinomas, 3-5% of tumors possess MET mutations. MET, is involved in activation of signaling pathways that regulate growth and mutations can result in prolonged MET activation leading to cancer development. Splicing errors can lead to MET exon-14 skipping, resulting in a hyper-active MET. While exon 14-deleted MET is a validated clinical target and FDA approved inhibitors are in use, development of resistance is common. Using genome editing technology, this study will generate the first ever atlas of MET exon 14 skipping variants, aiding in interpretation of clinical MET data. In addition, novel MET inhibitor resistance mechanisms will be identified with the goal of identifying combination therapies to overcome resistance to MET-targeted therapy.