**6. Acquired genetic alterations in melanoma**

Understanding the regulating pathways involved in melanoma development and progression has advanced significantly in recent years. The discovery of genetic alterations that aids in the formation of various cancers has aided in the development of numerous molecularly targeted therapies for individuals with metastatic disease [39,40,41]. These genes are known to be key molecular driver in melanoma; >70% cases harbor activating mutations in these genes. The molecule that is most commonly found to be mutated in melanomas is BRAF (~50% of all cancers) followed by NRAS (20%) and c-kit (1%) [42,43,44]. Melanoma is the result of complex changes in multiple signaling pathways affecting growth, cell mobility, metabolism and the ability to escape cell death progression. The Ras-Raf-Mek-Erk pathway followed by PI3K/Akt pathway is constitutively activated in a significant number of melanoma tumors.
