Research
BRAF is a serine threonine kinase that signals via the Mitogen Activated Protein Kinase Pathway. BRAF is one of the most frequently mutated oncogenes in cancer. The most common type of BRAF mutations are called BRAF V600 or Class 1 BRAF mutations. However, approximately 1/3 of all oncogenic mutations are non-V600 mutations, which can be classified as Class 2 or Class 3 BRAF mutations according to defined molecular characteristics. There are very effective targeted therapies (MAPK pathway inhibitors) that prolong survival and cure rates for patients with Class 1 BRAF mutant tumors. But unfortunately these same MAPK inhibitors are less effective against Class 2 & 3 BRAF mutant tumors. Our research focusses on these Class 2 and 3 BRAF mutations. Our goal is to develop novel therapeutic strategies that can be used to treat tumors that are driven by Class 2 & 3 BRAF mutations
NRAS is a GTPase and a protooncogene that is mutated and constitutively activated in 20-30% of metastatic melanomas. Currently, the only effective therapies for patients with NRAS mutant metastatic melanoma are immune checkpoint inhibitors. Patients with NRAS mutations are less likely to benefit from immune checkpoint inhibitors compared to patients with NRAS wildtype melanoma. We are using cancer cell lines, syngeneic mouse models and analyses of human melanoma tumors to try to figure out why NRAS mutant melanomas are more resistant to immune checkpoint inhibitors. We hope that our research will lead to new, effective treatments for patients with NRAS mutant melanoma.
Major Research Themes
Clinical trials to test novel MAPK inhibitor combinations in patients with non-V600 BRAF mutant cancer
Defining mechanisms of resistance to MAPK inhibitors in cancers with non-V600 BRAF mutations
Evaluating the role of mutant NRAS in mediating immunotherapy resistance in melanoma
Characterizing predictors of therapeutic response and resistance in genitourinary cancers
Research Funding
