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Detrimental effects of melanocortin‐1 receptor ( MC 1R) variants on the clinical outcomes of BRAF V600 metastatic melanoma patients treated with BRAF inhibitors
Author(s) -
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
Publication year - 2016
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12516
Subject(s) - metastatic melanoma , receptor , cancer research , melanoma , melanocortin 1 receptor , medicine , melanocortin , biology , phenotype , genetics , gene
Summary Melanocortin‐1 receptor ( MC 1R) plays a key role in skin pigmentation, and its variants are linked with a higher melanoma risk. The influence of MC 1R variants on the outcomes of patients with metastatic melanoma ( MM ) treated with BRAF inhibitors ( BRAF i) is unknown. We studied the MC 1R status in a cohort of 53 consecutive BRAF ‐mutated patients with MM treated with BRAF i. We also evaluated the effect of vemurafenib in four V600 BRAF melanoma cell lines with/without MC 1R variants. We found a significant correlation between the presence of MC 1R 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 IC 50 in MC 1R variant cell lines.