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

Michele Guida, Sabino Strippoli, Anna Ferretta, Nicola Bartolomeo, Letizia Porcelli, Immacolata Maida, Amalia Azzariti, Stefania Tommasi, Claudia Grieco, Stefania Guida, Anna Albano, Vito Lorusso, Gabriella Guida

Research output: Contribution to journalArticlepeer-review

Abstract

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 V600BRAF 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.

Original languageEnglish
Pages (from-to)679-687
Number of pages9
JournalPigment Cell and Melanoma Research
Volume29
Issue number6
DOIs
Publication statusPublished - Nov 1 2016

Keywords

  • BRAF inhibitors
  • Melanocortin-1 receptor
  • metastatic melanoma
  • predictive biomarkers

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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