B-RAF is a therapeutic target in melanoma.

M Karasarides, A Chiloeches, R Hayward, D Niculescu-Duvaz, I Scanlon, F Friedlos, L Ogilvie, D Hedley, J Martin, CJ Marshall, CJ Springer, R Marais

Research output: Contribution to journalArticlepeer-review


B-RAF is a serine/threonine-specific protein kinase that is mutated in approximately 70% of human melanomas. However, the role of this signalling molecule in cancer is unclear. Here, we show that ERK is constitutively activated in melanoma cells expressing oncogenic B-RAF and that this activity is required for proliferation. B-RAF depletion by siRNA blocks ERK activity, whereas A-RAF and C-RAF depletion do not affect ERK signalling. B-RAF depletion inhibits DNA synthesis and induces apoptosis in three melanoma cell lines and we show that the RAF inhibitor BAY43-9006 also blocks ERK activity, inhibits DNA synthesis and induces cell death in these cells. BAY43-9006 targets B-RAF signalling in vivo and induces a substantial growth delay in melanoma tumour xenografts. Our data demonstrate that oncogenic B-RAF activates ERK signalling, induces proliferation and protects cells from apoptosis, demonstrating that it is an important therapeutic target and thus provides novel strategies for clinical management of melanoma and other cancers.
Original languageEnglish
Pages (from-to)6292-6298
Number of pages7
Publication statusPublished - 21 Jun 2004


  • B-Raf
  • Melanoma
  • RNA interfernce


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