Molecular aspects of pancreatic cancer and future perspectives.
Pancreatic cancer has one of the worst prognoses of all human malignancies and the molecular mechanisms underlying this aggressive disease have been extensively investigated in the past years. Tyrosine kinase growth factor receptors and their ligands act to influence tumor cell growth, differentiation, invasion, metastasis, and angiogenesis. In pancreatic cancer a variety of these growth factor receptors and ligands are expressed at increased levels and this overexpression influences the clinical course of the disease. For example, the concomitant presence of the EGF receptor and its ligands EGF, TGF-alpha, and/or amphiregulin is associated with enhanced tumor aggressiveness and shorter survival periods following tumor resection. Furthermore, the growth inhibitory effects of the TGF-beta superfamily of serine-threonine kinase receptors and their ligands are often blocked in pancreatic cancer cells. In addition to these alterations, mutations of the p53 tumor-suppressor gene, the K-ras proto-oncogene, and the Smad4 gene are frequently present in these tumors. Taken together, the abundance of growth-promoting factors, the disturbance of growth inhibitory pathways, and the presence of gene mutations combine to give pancreatic cancer cells a distinct growth advantage which clinically results in rapid tumor progression and poor survival.
Friess
H
H
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Bern, Switzerland. helmut-friess@insel.ch
Kleeff
J
J
Korc
M
M
Büchler
M W
MW
D066246:ErbB Receptors / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D000090063:Proto-Oncogene Mas; D017978:Receptors, Growth Factor / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D018631:ras Proteins