[Pancreatic carcinogenesis. Clinical implications].
Our understanding of the molecular pathology of pancreatic carcinoma has improved tremendously over the past few years due to the development of sophisticated molecular techniques. This knowledge has led to the postulation of a pancreatic tumor progression model. This article describes the molecular oncogenesis of pancreatic carcinoma and points out potential targets for therapeutic interventions. Pancreatic cancer is characterized by the sequential acquisition of somatic mutations in the proto-oncogene K-RAS and the tumor suppressors INK4a,TP53 and DPC4/SMAD4 and by epigenetic alterations, including the overexpression of the "epidermal growth factor" receptor/ligand system. These genetic changes cause a profound disturbance to cell cycle regulation and continuous growth. Further analysis of the underlying molecular mechanisms will offer new diagnostic and therapeutic options and hopefully improve the outcome of this grim disease in the future.
Schneider
G
G
II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich.
Lersch
C
C
Schmid
R M
RM
D066246:ErbB Receptors / Q000235:genetics; D005544:Forecasting; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D011905:Genes, ras; D017228:Hepatocyte Growth Factor / Q000235:genetics; D006801:Humans; D009154:Mutation; D009857:Oncogenes; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D017228:Hepatocyte Growth Factor; D066246:ErbB Receptors; D018631:ras Proteins