Novel diagnostic and prognostic biomarkers and molecular therapeutic targets in aggressive, metastatic and recurrent melanomas

Cutaneous melanomas are the malignant and aggressive tumors of skin with extremely poor survival rates for the patients diagnosed with locally invasive and metastatic disease stages. Despite intensive research has led in last few years to an improvement of the curative treatment of early-stage cutaneous melanomas by tumor surgical resection, ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cell-based therapies, the locally advanced and disseminated melanomas are generally resistant to conventional therapies and result to the death of cancer patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease stages 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 frequently implicated in the malignant transformation of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during cancer initiation and progression to locally advanced and metastatic disease stages. These oncogenic events include the occurrence of activating mutations in distinct oncogenes such as v-Raf murine sarcoma viral oncogene homolog B1 (B-RAF) or neuroblastoma RAS viral oncogene homolog (N-Ras). The enhanced expression and activities of diverse growth factor signaling elements such as epidermal growth factor receptor (EGFR), sonic hedgehog, Wnt/β-catenin, Notch and vascular endothelial growth factor (VEGF)/VEGF-R receptors in melanoma cells also represent common molecular events associated with melanoma progression, metastases at distant sites, treatment resistance and disease relapse. Of therapeutic relevance, these deregulated signaling 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.