BRAFm+ Metastatic melanoma
What makes it different, makes it vulnerable

The role of BRAF and the MAP kinase pathway

The RAS/RAF/MEK/ERK pathway (also known as the MAP kinase pathway) is a critical pathway involved in normal cellular functions, but it may be disrupted in many human cancers, including melanoma.1,2

Signal transduction following activation of RAS and BRAF is mediated through the two MAP kinases (MEK1 and MEK2). Activated BRAF kinase phosphorylates MEK1/MEK2 via two regulatory serine residues. Activated MEK1/MEK2 phosphorylates threonine and serine residues on ERK1 and ERK2 (the only known substrates for MEK1 and MEK2).1,2

An image to represent the role of BRAF in the RAS/RAF/MEK/ERK signalling pathway

Phosphorylated ERK dimerises and translocates to the nucleus where it is involved in nuclear transport, DNA repair, nucleosome assembly, and mRNA processing and translation.1,2 Molecules involved in this RAS/RAF/MEK/ERK signal transduction pathway are therefore attractive targets for cancer therapies (See figure).

  1. Wellbrock C, et al. The RAF proteins take centre stage. Nat Rev Mol Cell Biol. 2004;5:875–85.
  2. Wan PTC, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell. 2004;116:855–67.