Melanoma: molecular pathogenesis and emerging target therapies (Review).
Malignant melanoma is an aggressive tumor of the skin with a poor prognosis for patients with advanced disease. It is resistant to current therapeutic approaches. In melanoma, both the Ras/Raf/MEK/ERK (MAPK) and the PI3K/AKT (AKT) signalling pathways are constitutively activated through multiple mechanisms. Mutations of BRAF have been proposed to contribute to melanoma development. Increased activity of the MAPK pathway prevents apoptosis and induces cell cycle progression. PTEN deletion results in Akt activation. Akt activation can result in the phosphorylation and inactivation of Raf. This decrease in downstream MEK and ERK activation may lead to loss of differentiation or senescence. This review summarizes the most relevant studies focused on the signalling pathways involved in melanomagenesis. New therapeutic strategies are also reported.
Department of Biomedical Sciences, University of Catania, I-95124 Catania, Italy.
Alessia E
AE
Russo
Elena
E
Torrisi
Ylenia
Y
Bevelacqua
Rosario
R
Perrotta
Massimo
M
Libra
James A
JA
McCubrey
Demetrios A
DA
Spandidos
Franca
F
Stivala
Grazia
G
Malaponte
D006801:Humans; D008545:Melanoma / Q000209:etiology* / Q000628:therapy*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000209:etiology* / Q000628:therapy*