The mitogen-activated protein kinase (MAPK) signaling pathway is evolutionarily conserved across the entire eukaryotic lineage, including plants, fungi and animals . Despite an in-depth understanding of the structure of the cascades and of their constituent parts, translating the language of signal transduction and the corresponding mitogenic response into a complete and predictable model has remained an enigma to biologists for over 30 years. The most important MAPK pathway in human cancer consists of a three-tiered hierarchy of serine-threonine kinases, RAF, MEK and ERK. To the best of our knowledge, RAF functions in this pathway as a signal transduction cypher, which algorithmically decodes the mitogenic stimuli to regulate cell division by activating the MAPK cascade . With the discovery of small molecule RAF inhibitors in the last decade, researchers have been able to solve part of this biochemical formula for RAF and MAPK activation, which opens new potential avenues for therapeutic intervention, and has already benefited patients with previously untreatable tumors.