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lüll PAR-4 as a possible new target for pancreatic cancer therapy Azmi AS; Philip PA; Zafar SF; Sarkar FH; Mohammad RMExpert Opin Ther Targets 2010[Jun]; 14 (6): 611-20IMPORTANCE OF THE FIELD: Pancreatic cancer (PC) is a deadly disease that is intractable to currently available treatment regimens. Although well described in different tumors types, the importance of apoptosis inducer prostate apoptosis response-4 (Par-4) in PC has not been appreciated. PC is an oncogenic kras driven disease, which is known to downregulate Par-4. Therefore, this review highlights its significance and builds a strong case supporting the role of Par-4 as a possible therapeutic target in PC. AREAS COVERED IN THIS REVIEW: Literature-based evidence spanning the last 15 years on Par-4 and its significance in PC. WHAT THE READER WILL GAIN: This review provides comprehensive knowledge of the significance of Par-4 and its association with kras status in PC, along with the crosstalk with crucial resistance and survival molecules NF-kappaB and Bcl-2 that ultimately are responsible for the overall poor outcome of different therapeutic approaches in this disease. TAKE HOME MESSAGE: Par-4 holds promise as a potential therapeutic target that can be induced by chemopreventive agents and small-molecule inhibitors either alone or in combination with standard chemotherapeutics leading to selective apoptosis in PC cells. It also acts as a chemosensitizer and therefore warrants further clinical investigations in this disease.|Animals[MESH]|Antineoplastic Agents/*pharmacology[MESH]|Apoptosis Regulatory Proteins/*metabolism[MESH]|Apoptosis/drug effects[MESH]|Drug Delivery Systems[MESH]|Humans[MESH]|Pancreatic Neoplasms/*drug therapy/physiopathology[MESH]|Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors/metabolism[MESH]|Proto-Oncogene Proteins p21(ras)[MESH]|Proto-Oncogene Proteins/metabolism[MESH]|ras Proteins/metabolism[MESH] |