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.
Boldt
Simone
S
Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden Glasgow G61 1BD, UK.
Kolch
Walter
W
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*
D004791:Enzyme Inhibitors; D020928:Mitogen-Activated Protein Kinases