Melanoma is the fifth most common cancer in the United States, with over 97,000 new cases diagnosed in 2023. Localized melanoma has favorable outcomes with a 5-year relative survival rate of 90%. However, metastatic melanoma remains difficult to treat, with a 5-year relative survival rate of 32%. These statistics emphasize the importance of trying to prevent the spread of melanoma (metastasis) and to improve treatment. Previous work has shown that a receptor located on the surface of melanoma tumor cells, called erythropoietin receptor (EPO-R), is associated with metastasis and drug resistance. Research from the field of blood cancer has shown that the interaction of EPO-R and a protein inside the cell called RasGPR3 causes blood stem cells to move into the bone marrow. Notably, recent work has shown that prior to metastasis, a small group of melanoma cells leave the tumor site on the skin and travel to the bone marrow. While in the bone marrow, these melanoma cells start to develop characteristics of the blood stem cells that are naturally found there. Given these findings, we propose that melanoma cells move into the bone marrow where their levels of EPO-R and RasGRP3 increase, which allows melanoma cells to migrate to different parts of the body (metastasize) and develop drug resistance. Previous work in our lab has allowed for the creation of a new compound, called URV3, that blocks EPO-R. In our studies, URV3 has been effective in preventing the movement of leukemia cells and blood stem cells. We aim to use URV3 to block EPO-R in melanoma cells and decrease cell movement by lowering EPO-R and RasGRP3 levels. We also predict that URV3 will increase the ability of melanoma cells to respond to treatment.