Pancreatic cancer has one of the poorest prognoses of all gastrointestinal
malignancies. Today, it is the fourth or fifth leading cause of
cancer-related deaths in Western industrialized countries, and the incidence has been increasing throughout the past decades. Insensitivity to growth-inhibitory and apoptotic signals as well as self-sufficiency of growth-promoting factors are hallmarks of the pathogenesis of this
malignancy. In
pancreatic cancer, a variety of
growth factors and their receptors are expressed at increased levels. For example, the concomitant presence of the
epidermal growth factor (
EGF) receptor and its
ligand EGF is associated with enhanced
tumor aggressiveness and shorter survival following
tumor resection. Furthermore, a number of other
growth factors and their receptors, such as
nerve growth factor and its receptor, are overexpressed in
pancreatic cancer and contribute to its malignant phenotype. Besides factors which directly promote cell proliferation, a variety of other factors such as
galectins are upregulated, which influences the
tumor environment and the invasiveness of
pancreatic cancer cells. In addition, tumor suppressor genes such as KAI1 are expressed at reduced levels, thereby enhancing the ability of pancreatic cells to form
metastases. A complex disturbance of factors is present in
pancreatic cancer, resulting in a distinct growth advantage which clinically results in rapid
tumor progression and poor patient survival.