Targeting MAPK signalling: Prometheus' fire or pandora's box?

MAPK (Mitogen Activated Protein Kinase) pathways mediate fundamental biological processes and have moved into the limelight of drug discovery during the past decade. Here we review the biochemistry and biology of MAPK signalling with a focus on ERK, JNK and p38. We summarise current drug discovery efforts and clinical trials. Further, we critically discuss the rationale behind current strategies of using MAPK pathways as drug targets and suggest new approaches that take the complexity of MAPK signalling networks into account.