title: Multiple Molecular Pathways in Melanomagenesis: Characterization of Therapeutic Targets.
abstract: Molecular mechanisms involved in pathogenesis of malignant melanoma have been widely studied and novel therapeutic treatments developed in recent past years. Molecular targets for therapy have mostly been recognized in the RAS-RAF-MEK-ERK and PI3K-AKT signaling pathways; small-molecule inhibitors were drawn to specifically target key kinases. Unfortunately, these targeted drugs may display intrinsic or acquired resistance and various evidences suggest that inhibition of a single effector of the signal transduction cascades involved in melanoma pathogenesis may be ineffective in blocking the tumor growth. In this sense, a wider comprehension of the multiple molecular alterations accounting for either response or resistance to treatments with targeted inhibitors may be helpful in assessing, which is the most effective combination of such therapies. In the present review, we summarize the known molecular mechanisms underlying either intrinsic and acquired drug resistance either alternative roads to melanoma pathogenesis, which may become targets for innovative anticancer approaches.
authors: Unità di Genetica dei Tumori, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche , Sassari , Italy.
authors: Giuseppe
authors: G
authors: Palmieri
authors: Istituto di Scienze dell'Alimentazione, Consiglio Nazionale delle Ricerche , Avellino , Italy.
authors: MariaNeve
authors: M
authors: Ombra
authors: Unità di Genetica dei Tumori, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche , Sassari , Italy.
authors: Maria
authors: M
authors: Colombino
authors: Unità di Genetica dei Tumori, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche , Sassari , Italy.
authors: Milena
authors: M
authors: Casula
authors: Unità di Genetica dei Tumori, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche , Sassari , Italy.
authors: MariaCristina
authors: M
authors: Sini
authors: Unità di Genetica dei Tumori, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche , Sassari , Italy.
authors: Antonella
authors: A
authors: Manca
authors: Dipartimento di Scienze Chirurgiche, Microchirurgiche e Mediche, Università di Sassari , Sassari , Italy.
authors: Panagiotis
authors: P
authors: Paliogiannis
authors: Istituto Nazionale Tumori "Fondazione Pascale" , Naples , Italy.
authors: Paolo Antonio
authors: PA
authors: Ascierto
authors: Dipartimento di Scienze Chirurgiche, Microchirurgiche e Mediche, Università di Sassari , Sassari , Italy.
authors: Antonio
authors: A
authors: Cossu
keywords: alternative therapeutic targets; melanoma pathogenesis; molecular melanoma classification; signal transduction cascades; targeted-therapy resistance