PAR-4 as a possible new target for pancreatic cancer therapy

Importance 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-kappa B 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.