Melanoma is the less common but the most malignant skin cancer.,Since the survival rate of melanoma metastasis is about 10-15%, many different studies have been carried out in order to find a more effective treatment.,Although the development of target-based therapies and immunotherapeutic strategies has improved chances for patient survival, melanoma treatment still remains a big challenge for oncologists.,Here, we collect recent data about the emerging role of melanoma-associated microRNAs (miRNAs) currently available treatments, and their involvement in drug resistance.,We also reviewed miRNAs as prognostic factors, because of their chemical stability and resistance to RNase activity, in melanoma progression.,Moreover, despite miRNAs being considered small conserved regulators with the limitation of target specificity, we outline the dual role of melanoma-associated miRNAs, as oncogenic and/or tumor suppressive factors, compared to other tumors.
Mitogen activated-protein kinase pathway inhibitors (MAPKis) improve treatment outcome in patients with disseminated BRAFV600 mutant cutaneous malignant melanoma (CMM) but responses are of limited duration due to emerging resistance.,Although extensive research in mechanisms of resistance is being performed, predictive biomarkers for durable responses are still lacking.,We used miRNA qPCR to investigate if different levels of extracellular microvesicle microRNA (EV miRNA) in matched plasma samples collected from patients with metastatic IV BRAFV600 mutated CMM before, during and after therapy with MAPKis could serve as predictive biomarkers.,EV miRNAs were extracted from plasma samples from 28 patients collected before and during therapy, measured by quantitative PCR-array and correlated to therapy outcome.,Increased levels of EV let-7g-5p during treatment compared to before treatment (EV let-7g-5p_delta) were associated with better disease control with MAPKis (odds ratio 8568.4, 95% CI = 4.8-1.5e+07, P = 0.000036).,Elevated levels of EV miR-497-5p during therapy were associated with prolonged progression free survival (PFS) (hazard ratio = 0.27, 95% CI = 0.13-0.52, P <0.000061).,EV miRNAs let-7g-5p and miR-497-5p were identified as putative novel predictive biomarkers of MAPKi treatment benefit in metastatic CMM patients highlighting the potential relevance of assessing EV miRNA during and after treatment to unravel novel mechanisms of resistance.