Detrimental effects of melanocortin‐1 receptor (MC1R) variants on the clinical outcomes of BRAF V600 metastatic melanoma patients treated with BRAF inhibitors. (November 2016)

• Record Type: Journal Article
• Authors: Guida, Michele; Strippoli, Sabino; Ferretta, Anna; Bartolomeo, Nicola; Porcelli, Letizia; Maida, Immacolata; Azzariti, Amalia; Tommasi, Stefania; Grieco, Claudia; Guida, Stefania; Albano, Anna; Lorusso, Vito; Guida, Gabriella
• Is Part Of: Pigment cell & melanoma research. Volume 29:Number 6(2016:Nov.)
• Page Start: 679
• Page End: 687
• Publication Date: 2016-11
• Subjects: Melanocortin‐1 receptor -- BRAF inhibitors -- metastatic melanoma -- predictive biomarkers; Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12516
• Languages: English
• ISSNs: 1755-1471

Abstract

Summary: Melanocortin‐1 receptor (MC1R) plays a key role in skin pigmentation, and its variants are linked with a higher melanoma risk. The influence of MC1R variants on the outcomes of patients with metastatic melanoma (MM) treated with BRAF inhibitors (BRAFi) is unknown. We studied the MC1R status in a cohort of 53 consecutive BRAF‐mutated patients with MM treated with BRAFi. We also evaluated the effect of vemurafenib in four V600 BRAF melanoma cell lines with/without MC1R variants. We found a significant correlation between the presence of MC1R variants and worse outcomes in terms of both overall response rate (ORR; 59% versus 95%, P = 0.011 univariate, P = 0.028 multivariate analysis) and progression‐free survival (PFS) shorter than 6 months (72% versus 33%, P = 0.012 univariate, P = 0.027 multivariate analysis). No difference in overall survival (OS) was reported, probably due to subsequent treatments. Data in vitro showed a significant different phosphorylation of Erk1/2 and p38 MAPK during treatment, associated with a greater increase in vemurafenib IC50 in MC1R variant cell lines.