Cutaneous malignant melanoma is the most aggressive form of skin cancer with an 
extremely poor survival rate for the patients diagnosed with locally invasive 
and metastatic disease states. Intensive research has led in last few years to 
an improvement of the early detection and curative treatment of primary 
cutaneous melanomas that are confined to the skin by tumor surgical resection. 
However, locally advanced and disseminated melanomas are generally resistant to 
conventional treatments, including ionizing radiation, systemic chemotherapy, 
immunotherapy and/or adjuvant stem cell-based therapies, and result in the death 
of patients. The rapid progression of primary melanomas to locally invasive 
and/or metastatic disease states remains a major obstacle for an early effective 
diagnosis and a curative therapeutic intervention for melanoma patients. 
Importantly, recent advances in the melanoma research have led to the 
identification of different gene products that are often implicated in the 
malignant transformation of melanocytic cells into melanoma cells, including 
melanoma stem/progenitor cells, during melanoma initiation and progression to 
locally advanced and metastatic disease states. The frequent deregulated genes 
products encompass the oncogenic B-RafV600E and N-RasQ61R mutants, different 
receptor tyrosine kinases and developmental pathways such as epidermal growth 
factor receptor (EGFR), stem cell-like factor (SCF) receptor KIT, hedgehog, 
Wnt/β-catenin, Notch, stromal cell-derived factor-1 (SDF-1)/CXC chemokine 
receptor-4 (CXCR4) and vascular endothelial growth factor (VEGF)/VEGFR receptor. 
These growth factors can cooperate to activate distinct tumorigenic downstream 
signaling elements and epithelial-mesenchymal transition (EMT)-associated 
molecules, including phosphatidylinositol 3'-kinase (PI3K)/Akt/ molecular target 
of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), macrophage inhibitory 
cytokine-1 (MIC-1), vimentin, snail and twist. Of therapeutic relevance, these 
deregulated signal transduction components constitute new potential biomarkers 
and therapeutic targets of great clinical interest for improving the efficacy of 
current diagnostic and prognostic methods and management of patients diagnosed 
with locally advanced, metastatic and/or relapsed melanomas.