title: [Tyrosine kinase receptor-ras-ERK signal transduction pathway as therapeutic tarfet in cancer].
abstract: BACKGROUND
  Experimental evidence indicates that various intracellular signalling cascades are altered in tumour cells. Among these, the receptor tyrosine kinase ras-ERK signalling pathway was found to be constitutively active in a significant percentage of human tumours; hence, considerable effort has been directed at finding compounds that inhibit its activation.
  
  
  METHODS
  We review the recent progress in establishing novel approaches to interference with the constitutive activation of the receptor tyrosine kinase ras-ERK signalling pathway in cancer.
  
  
  RESULTS
  Inhibition of the receptor tyrosine kinase ras-ERK signalling pathway activation by various novel agents (e.g. small molecule tyrosine kinase inhibitors, antibodies, FTase inhibitors, SH2/SH3 directed agents, antisense, ribozymes) impaired tumour growth. Some of the developed agents have been tested in clinical trials; promising results were obtained.
  
  
  CONCLUSIONS
  Inactivation of the receptor tyrosine kinase ras-ERK signalling pathway by small molecular inhibitors has confirmed its involvement in tumour growth. Thus, molecular and/or pharmacological modulation of the components that are critically involved in the constitutive activation of this pathway are expected to improve the treatment of human malignancies.
authors.affiliation: Avdeling for immunologi Gruppe for molekylaer medisin Institutt for Kreftforskning Det Norske Radiumhospital Montebello 0310 Oslo. marianne.leirdal@labmed.uio.no
authors.forename: Marianne
authors.initials: M
authors.lastname: Leirdal
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011905:Genes, ras; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009696:Nucleic Acids / Q000235:genetics / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009696:Nucleic Acids; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases