The role of Raf kinases in malignant transformation.

The Raf kinases are proto-oncogenes that work at the entry point of the mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway, a signalling module that connects cell-surface receptors and Ras proteins to nuclear transcription factors. The pathway impinges on all the functional hallmarks of cancer cells: immortalisation, growth-factor-independent proliferation, insensitivity to growth-inhibitory signals, ability to invade and metastasise, ability to attract blood vessels, and evasion of apoptosis. Indeed, the pathway is hyperactivated in 30% of all human tumours including prevalent cancers of the colon and lung. The molecular mechanisms underlying the role of Raf kinase in tumourigenesis and the opportunities for therapeutic intervention are reviewed in this article.