Grant: Project Grant

Melanoma is the deadliest form of skin cancer, and while current treatments have improved outcomes, many patients with advanced disease still face poor survival rates. One of the main causes of melanoma is the abnormal activation of the RAS/MAPK signaling pathway, which controls how cancer cells grow and spread. Although treatments targeting this pathway have been developed, melanoma cells often become resistant to these therapies, leading to disease progression. This highlights the need for new treatment strategies. In addition to genetic changes, recent research suggests that epigenetic alterations - changes in how genes are turned on or off without altering the DNA itself - play a crucial role in melanoma development and resistance to therapy. However, the exact mechanisms of how epigenetic factors influence melanoma are still not well understood. Our research focuses on BRD2, a protein that regulates gene expression by binding to specific regions of DNA. We have found that the RAS/MAPK pathway causes BRD2 to be modified by another protein called MSK, which adds a phosphate group to BRD2. This modification appears to enhance BRD2's ability to promote the growth of melanoma cells. However, the exact role of this modification in melanoma progression is not yet known. The goal of this project is to understand how this modification of BRD2 affects melanoma growth and spread. We will first investigate how BRD2 is modified in melanoma cells. Next, we will explore how this modification changes BRD2's ability to control gene expression. Finally, we will study how these changes influence the ability of melanoma cells to grow and spread in laboratory models and in human tissue samples. By better understanding how BRD2 functions in melanoma, we hope to identify new targets for therapy that could improve treatment options for patients with advanced melanoma.