Melanoma Cell Signalling: Looking Beyond RAS-RAF-MEK

摘要: Melanoma is an invasive and malignant form of skin cancer (Besaratinia Pfeifer, 2008). It originates from melanocytes, which reside in the epidermal layer skin. Besides skin, melanoma’s rapidly proliferative aggressive nature leads to its manifestation internal organs such as brain, lung liver (Franco-Lie et al., 2011; Lejeune 1992). Ultraviolet (UV) radiation (sunlight or tanning beds) main carcinogen involved melanoma development. However, type (UVA versus UVB) duration UV (intermittent chronic childhood sun exposure) necessary for initiation remains ambiguous (Algazi 2010; Besaratinia 2008; Lazovich Walker, In addition, presence melanocytic nevi hereditary genetic mutations predisposes individuals (Navarini Pho Leachman, Whiteman 2003). As a result these factors, it estimated that 132,000 cancers occur annually (World Health Organization [WHO], 2011). This value set rise by 4,500 incidences every 10% decrease UV-protective ozone levels (WHO, Prevention strategies designed curtail onset improved treatment this evolving anomaly require urgent action. Current treatments adjuvant therapies includes, surgical excision, radio-, chemoand immunotherapy (Dummer Petrescu 2010). with recurrence melanomas, spotlight on molecular targeted therapy. Such depth knowledge signalling treat cancer. Molecular therapy has focused predominantly RAS-RAF-MEK [mitogen activated protein kinase (MAPK)-extracellular signal-regulated (ERK) kinase] phosphoinositide-3-kinase (PI3K)/AKT pathways Friedlander Hodi, Held Sullivan Atkins, due complex network pathways, become evident targeting single eradicate insufficient (Table 1) (Jiang Johannessen Nazarian Shields 2007). al. (2007) found distinct subset cell lines did not exhibit high ERK AKT activation but had increased expression epithelial markers like P-cadherin, E-cadherin CD24. These epithelial-like also loss p53 function, decreased microphthalmia-associated transcription factor (MITF) gene expression. Recent studies have shown many subsets cells resistance B-RAF inhibitors