Targeting the ERK signaling pathway in melanoma

Paola Savoia, Paolo Fava, Filippo Casoni, Ottavio Cremona

Research output: Contribution to journalReview articlepeer-review


The discovery of the role of the RAS/RAF/MEK/ERK pathway in melanomagenesis and its progression have opened a new era in the treatment of this tumor. Vemurafenib was the first specific kinase inhibitor approved for therapy of advanced melanomas harboring BRAF-activating mutations, followed by dabrafenib and encorafenib. However, despite the excellent results of first-generation kinase inhibitors in terms of response rate, the average duration of the response was short, due to the onset of genetic and epigenetic resistance mechanisms. The combination therapy with MEK inhibitors is an excellent strategy to circumvent drug resistance, with the additional advantage of reducing side effects due to the paradoxical reactivation of the MAPK pathway. The recent development of RAS and extracellular signal-related kinases (ERK) inhibitors promises to add new players for the ultimate suppression of this signaling pathway and the control of pathway-related drug resistance. In this review, we analyze the pharmacological, preclinical, and clinical trial data of the various MAPK pathway inhibitors, with a keen interest for their clinical applicability in the management of advanced melanoma.

Original languageEnglish
Article number1483
JournalInternational Journal of Molecular Sciences
Issue number6
Publication statusPublished - Mar 2 2019


  • BRAF inhibitors
  • ERK inhibitors
  • ERK pathway
  • MEK inhibitors
  • Melanoma treatment
  • Metastatic melanoma
  • NRAS inhibitors
  • Target therapy

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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