Ras/Raf signalling and emerging pharmacotherapeutic targets.

The Ras-Raf-MEK-ERK pathway is a ubiquitously expressed signalling module that regulates the proliferation, differentiation and survival of cells. This pathway features several oncogenes and is deregulated in approximately 30% of all human cancers. Thus, it has emerged as a prime target for antitumour therapy. Drugs targeting Ras, Raf or MEK are currently in clinical trials. They comprise vaccines, isoprenylation inhibitors, antisense compounds and kinase inhibitors. Most are remarkably well tolerated and some show promising efficacy. However, it is not clear which components of this pathway should be targeted and how maximum efficacy can be achieved. This paper reviews the current efforts with an emphasis on new mechanistic and conceptual approaches.