Clinical implications of acquired braf inhibitors resistance in melanoma

Paola Savoia, Elisa Zavattaro, Ottavio Cremona

Research output: Contribution to journalReview articlepeer-review

Abstract

Understanding the role of mitogen-activated protein kinase (MAPK) pathway-activating mutations in the development and progression of melanoma and their possible use as therapeutic targets has substantially changed the management of this neoplasm, which, until a few years ago, was burdened by severe mortality. However, the presence of numerous intrinsic and extrinsic mechanisms of resistance to BRAF inhibitors compromises the treatment responses’ effectiveness and durability. The strategy of overcoming these resistances by combination therapy has proved successful, with the additional benefit of reducing side effects derived from paradoxical activation of the MAPK pathway. Furthermore, the use of other highly specific inhibitors, intermittent dosing schedules and the association of combination therapy with immune checkpoint inhibitors are promising new therapeutic strategies. However, numerous issues related to dose, tolerability and administration sequence still need to be clarified, as is to be expected from currently ongoing trials. In this review, we describe the clinical results of using BRAF inhibitors in advanced melanoma, with a keen interest in strategies aimed at overcoming resistance.

Original languageEnglish
Article number9730
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number24
DOIs
Publication statusPublished - Dec 2 2020

Keywords

  • BRAF inhibitors
  • Metastatic melanoma
  • Resistance
  • 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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