Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids
Schematic summary of the most common mutations found in melanoma patients. The most common risk for melanoma is UV, and most DNA alterations are typically UV-induced. Family history of melanoma accounts for a two-fold risk increase, through mutations at the level of CDKN2A gene. These often affect the tumor suppressors p16INK4a or p14ARF, which have roles in the cell cycle and apoptosis, respectively. On the other hand, there is the RAS/RAF signaling pathway, which importance is underlined by the fact that exclusively NRAS or BRAF is mutated in melanoma. However, the presence of BRAF mutations in benign nevi suggest that BRAF per se does not suffice for the tumor progression. Often mutations in PTEN pathways have been found to cooperate with RAS/RAF to reduce RAS/RAF-mediated senescence.