Is Knowledge About the Genetic and Epigenetic Alterations in Melanoma a Basis for Targeted Therapy?

Melanoma, a deadly form of skin cancer, showed little therapeutic advancement over 30 years, with Dacarbazine being the only FDA-approved chemotherapy, offering limited efficacy. Genetic and epigenetic alterations, particularly in the MAPK and PI3K/Akt pathways, were identified as key drivers of melanoma, with common mutations in BRAF and N-Ras. Despite promising in vitro results for inhibitors targeting these pathways, early clinical trials showed limited success, suggesting the need for targeting multiple pathways simultaneously to overcome resistance. The tumor microenvironment was also recognized as a significant factor in therapeutic response, highlighting the importance of developing better melanoma models and understanding genetic mutations for effective targeted therapy.