PMID- 12566895
OWN - NLM
STAT- MEDLINE
DCOM- 20030423
LR  - 20220410
IS  - 0378-584X (Print)
IS  - 0378-584X (Linking)
VI  - 25
IP  - 6
DP  - 2002 Dec
TI  - The Ras-Raf-MEK-ERK pathway in the treatment of cancer.
PG  - 511-8
AB  - The mitogen activated protein kinases (MAPKs) are conserved proteins that 
      regulate cell growth, division and death. Although activated in the cytosol, the 
      MAPKs translocate to the nucleus upon activation and phosphorylate a large number 
      of nuclear proteins. Investigating how Ras transmits extracellular growth 
      signals, the MAPK pathway has emerged as the crucial route between membrane-bound 
      Ras and the nucleus. The MAPK pathway represents a cascade of phosphorylation 
      events including three pivotal kinases, namely Raf, MEK (MAP kinase kinase), and 
      ERK (MAP kinase). These kinases present new opportunities for the development of 
      novel anti-cancer drugs designed to be target-specific and probably less toxic 
      than conventional chemotherapeutic agents. A number of drugs inhibiting Ras, Raf 
      or MEK are currently under clinical investigation. This review addresses the 
      rationale for targeting the MAP kinase pathway and the current status of various 
      pharmacological approaches.
CI  - Copyright 2002 S. Karger GmbH, Freiburg
FAU - Hilger, R A
AU  - Hilger RA
AD  - Department of Internal Medicine and Medical Oncology, West German Cancer Center, 
      University Medical School of Essen, Germany.
FAU - Scheulen, M E
AU  - Scheulen ME
FAU - Strumberg, D
AU  - Strumberg D
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Switzerland
TA  - Onkologie
JT  - Onkologie
JID - 7808556
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
RN  - EC 2.7.11.25 (MAP3K1 protein, human)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Cell Division/*drug effects/physiology
MH  - Cell Survival/drug effects/physiology
MH  - Clinical Trials, Phase I as Topic
MH  - Humans
MH  - *MAP Kinase Kinase Kinase 1
MH  - Mitogen-Activated Protein Kinases/*antagonists & inhibitors/physiology
MH  - Neoplasms/*drug therapy/physiopathology
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors/physiology
MH  - Proto-Oncogene Proteins c-raf/*antagonists & inhibitors/physiology
MH  - Proto-Oncogene Proteins p21(ras)/*antagonists & inhibitors/physiology
MH  - Signal Transduction/*drug effects/physiology
RF  - 83
EDAT- 2003/02/05 04:00
MHDA- 2003/04/24 05:00
CRDT- 2003/02/05 04:00
PHST- 2003/02/05 04:00 [pubmed]
PHST- 2003/04/24 05:00 [medline]
PHST- 2003/02/05 04:00 [entrez]
AID - 68621 [pii]
AID - 10.1159/000068621 [doi]
PST - ppublish
SO  - Onkologie. 2002 Dec;25(6):511-8. doi: 10.1159/000068621.