Growth factors and their receptors in pancreatic cancer

Pancreatic cancer has an incidence of approximately 8 to 10 cases per 100,0 00 citizens in Western industrialized countries, and the incidence has been increasing throughout the last decades. Insensitivity to antigrowth and ap optotic signals as well as self-sufficiency in growth signals are hallmarks of malignant growth. Pancreatic cancers often exhibit alterations in growt h inhibitory pathways such as Smad4 mutations and Smad6 and Smad7 overexpre ssion, and evade apoptosis through p53 mutations and aberrant expression of apoptosis regulating genes. In addition, in pancreatic cancer a variety of growth factors are expressed at increased levels. For example, the concomi tant presence of the EGF-receptor and its ligands EGF TGF-alpha, and/or amp hiregulin is associated with enhanced tumor aggressiveness and shorter surv ival periods following tumor resection. Furthermore, a number of other grow th factors and their receptors, such as fibroblast growth factors, nerve gr owth factor, platelet-derived growth factors, and insulin-like growth facto rs and their respective receptors are expressed at increased levels in panc reatic cancer and are thought to contribute to its malignant phenotype. Tak en together, the disturbance of growth inhibitory and apoptotic pathways an d the abundance of growth promoting factors give pancreatic cancer cells a distinct growth advantage which clinically results in rapid tumor progressi on and poor survival prognosis. Teratogenesis Carcinog. Mutagen. 21:27-44, 2001. (C) 2001 Wiley-Liss, Inc.