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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism*
  • Drug Delivery Systems
  • Humans
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / physiopathology
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins / metabolism

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • prostate apoptosis response-4 protein
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins