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Expert Opin Ther Targets. 2010 Jun;14(6):611-20. doi: 10.1517/14728222.2010.487066.

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

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  • 1Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA. azmia@karmanos.org

Abstract

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-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.

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