Pancreatic cancer--new aspects of molecular biology research.
Pancreatic ductal adenocarcinoma (PDAC) presently has an incidence of approximately 8 to 10 cases per 100,000 citizens in European countries, and the incidence has been increasing throughout the last decades. Approximately 30,000 patients die every year from PDAC in Western Europe and most of the newly diagnosed patients present with an already unresectable tumor stage. Self-sufficiency in growth signals, insensitivity to antigrowth signals, and evasion of apoptosis are hallmarks of malignant growth. In PDAC a variety of growth factors are expressed at increased levels. 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. In addition, PDACs often exhibit alterations in growth inhibitory pathways such as Smad4 mutations and Smad6 and Smad7 overexpression, and evade apoptosis through p53 mutations and aberrant expression of apoptosis regulating genes such as members of the Bcl family. Taken together, the abundance of growth promoting factors and the disturbance of growth inhibitory and apoptotic pathways give pancreatic cancer cells a distinct growth advantage which clinically results in rapid tumor progression and poor survival prognosis.
Kleeff
J
J
Department of Visceral and Transplantation Surgery, University of Berne, Inselspital.
Friess
H
H
Berberat
P O
PO
Martignoni
M E
ME
Z'graggen
K
K
Büchler
M W
MW
D017209:Apoptosis / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D010179:Pancreas / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
D006133:Growth Substances