Project 460122

Metastatic melanoma is a devastating and deadly disease. Fortunately, great strides have been made in the treatment of melanoma and a number of effective treatments are now available to patients. Some of these treatments, including immunotherapies and targeted therapies can even lead to cures. However, not all melanoma patients derive the same benefit from these current standard therapies. Melanoma can be categorized according to the presence or absence of mutations in certain genes. The gene NRAS is mutated in 20-30% of all metastatic melanomas. We found that patients with NRAS mutant melanoma experienced less benefit and shorter survival when treated with standard immunotherapies. There are no effective treatment options for patients with NRAS mutant melanoma who don't respond to immunotherapy. Therefore more research is needed to develop better treatments for patients with NRAS mutant melanoma. For this project, we have three main aims: 1) Characterize the differences in immune cell populations between NRAS mutant and wildtype melanomas 2) Investigate whether NRAS signalling within tumor cells to dictates response to immunotherapy 3) Develop new and more effective combination immune-genomic therapies that are tailor made to specifically treat NRAS mutant melanomas. Together with these experiments and analyses, we plan to create new treatments for NRAS mutant melanoma. The goal is to bring these new treatments to patients in clinical trials. Ultimately, we hope to improve survival rates and cure rates for patients with NRAS mutant metastatic melanoma.