Growth factors and their receptors in pancreatic cancer.

Pancreatic cancer has an incidence of approximately 8 to 10 cases per 100,000 citizens in Western industrialized countries, and the incidence has been increasing throughout the last decades. Insensitivity to antigrowth and apoptotic signals as well as self-sufficiency in growth signals are hallmarks of malignant growth. Pancreatic cancers 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. In addition, in pancreatic cancer 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. Furthermore, a number of other growth factors and their receptors, such as fibroblast growth factors, nerve growth factor, platelet-derived growth factors, and insulin-like growth factors and their respective receptors are expressed at increased levels in pancreatic cancer and are thought to contribute to its malignant phenotype. Taken together, the disturbance of growth inhibitory and apoptotic pathways and the abundance of growth promoting factors give pancreatic cancer cells a distinct growth advantage which clinically results in rapid tumor progression and poor survival prognosis.