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[Resistance to BRAF inhibitors: A lesson from clinical observations].

Cylia DahmaniEulalie CorreSarah DandouAlain MangéOvidiu RadulescuPeter J CoopmanPierre CuqRomain Maxime Larive
Published in: Medecine sciences : M/S (2022)
The MAPK/ERK pathway is an essential intracellular signaling pathway. Its deregulation is involved in tumor transformation and progression. The discovery of activating mutations of BRAF in various cancers has opened new therapeutic avenues with BRAF protein kinase inhibitors. Depending on the type of cancers, these inhibitors have shown either insufficient efficacy due to primary resistance of tumor cells or transient efficacy due to the development of acquired resistance. In this review, we revisit the discoveries that led to the development of BRAF inhibitors and detail the molecular and cellular mechanisms of resistance in cancers treated with these inhibitors. Understanding these mechanisms is crucial for developing more efficient therapeutic strategies.
Keyphrases
  • signaling pathway
  • pi k akt
  • metastatic colorectal cancer
  • wild type
  • oxidative stress
  • small molecule
  • epithelial mesenchymal transition
  • high throughput
  • binding protein
  • reactive oxygen species
  • light emitting