Frederick Wilson, MD, PhD

Dr. Wilson's research efforts broadly include cancer genomics, identifying cancer vulnerabilities, and understanding resistance to targeted therapies. Specific areas of interest include:

1. Characterization of RASGRF1 fusions as an oncogenic driver in lung and other cancers. Dr. Wilson’s team identified recurrent gene fusions involving the guanine exchange factor (GEF) RASGRF1 in non-small cell lung cancer, pancreatic ductal adenocarcinoma, and sarcoma. RASGRF1 fusions activate RAS signaling, induce cellular transformation, and promote tumorigenesis. Preclinical studies demonstrate that tumor cells harboring RASGRF1 fusions are sensitive to targeting of the MAP kinase pathway, an established downstream effector of RAS signaling.

2. PRMT5 pathway inhibition as a therapeutic strategy in cancers with MTAP loss. Deletion of the MTAP gene occurs in approximately 15% of all malignancies. Dr. Wilson and others identified the arginine methyltransferase PRMT5 as a potential genetic vulnerability in cancers with MTAP loss, suggesting that these cancers may be sensitive to targeting of PRMT5. This work provided a rationale for the development of inhibitors of PRMT5 and MAT2A (another pathway component) which are entering early-phase clinical study in patients with advanced MTAP-deleted cancers.

3. Resistance to targeted therapies in lung cancer. Multiple FDA-approved targeted therapies are available for patients with advanced non-small cell lung cancer with mutated oncogenic drivers including EGFR, ALK, and ROS1. Unfortunately, resistance to these therapies is common and limits the ability to provide durable cancer control for patients. Using a genome-scale functional genomic screening platform, Dr. Wilson identified novel genetic drivers of resistance to ALK inhibitors in ALK-dependent lung cancer models. Many of the resistance-associated genes identified from this study also confer resistance to EGFR inhibition in EGFR-mutant lung cancer models. Insights from these studies may inform the development of treatment paradigms to delay or overcome resistance to targeted therapies in patients with advanced lung cancers.

Ultimately, translational research efforts in the laboratory are directed towards the identification of novel drug targets and opportunities for therapeutic drug combinations to overcome or delay drug resistance.