Anti-angiogenesis therapy in pancreatic carcinoma

Pancreatic adenocarcinoma is a leading cause of cancer death in the United States and represents a challenging chemotherapeutic problem. The treatment of advanced pancreatic cancer with gemcitabine has only modest activity with a small survival benefit, and toxicity continues to be a major obstacle. New therapeutic strategies that notably lack cross resistance with established treatment regimens are much needed in pancreatic cancer. One such approach is the pharmacological control of angiogenesis that represents a novel approach to the management of pancreas cancer, since the pathological development of vascular supply is a critical step for tumor growth and may affect its prognosis. Since pancreatic carcinoma show strong tumor neoangiogenesis, overexpression of vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, in pancreatic cancer and consequently are highly vascularized, the role of anti-angiogenic therapies is under exploration at present. Hence, this review covers the summary of the development of anti-angiogenesis as anti-antitumor therapy in pancreatic carcinoma, including matrix-metalloproteinase inhibitors (MMPIs), such as marimastat and BAY 12-9566, anti-VEGF agent, bevacizumab (Avastin, Genentech, South San Francisco, CA, USA), celecoxib (a cyclooxygenase-2 inhibitor), thalidomide and others. Role of markers of angiogenesis in predicting response to therapy is also discussed.