Integrin-based therapy of pancreatic adenocarcinoma: current status and future perspectives

Pancreatic ductal adenocarcinoma (PDAC), although tenth in cancer incidence, holds the dubious distinction of being the fifth cause of cancer deaths in the Western countries and possibly the deadliest malignancy. Inoperable PDAC is characterized by late diagnosis, extensive metastases, extremely poor response to chemotherapy and, consequently, poor patients' prognosis-6.7% 5-year survival. PDAC reflects the failure of the medical profession to significantly prolong patients' lives and modest expectations for future cure. PDAC is characterized by extensive desmoplastic reaction, resulting in approximately 50% of tumor's volume consisting of non-tumor cells and extracellular matrix (ECM) stroma. These properties imply an important role for cell-ECM interaction, making cell-matrix adhesion molecules, such as integrins, of special interest as possible candidate targets for future anti-PDAC therapies. This review will attempt to overview the status of studies dealing with the involvement of integrins in the unique aggressive character of PDAC, the current status of experimental cancer therapies targeted at integrins, and the possible application of these preliminary clinical experiments to future PDAC therapy. I will also try to delineate the reasons for the failures of PDAC therapies and make some modest suggestions that might improve the health scientific community approaches to this extremely difficult problem.