Apoptotic pathways in pancreatic ductal adenocarcinoma

Mol Cancer. 2008 Jul 24;7:64. doi: 10.1186/1476-4598-7-64.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most common causes of cancer related death. Despite the advances in understanding of the molecular pathogenesis, pancreatic cancer remains a major unsolved health problem. Overall, the 5-year survival rate is less than 5% demonstrating the insufficiency of current therapies. Most cytotoxic therapies induce apoptosis and PDAC cells have evolved a plethora of molecular mechanisms to assure survival. We will present anti-apoptotic strategies working at the level of the death receptors, the mitochondria or involving the caspase inhibitors of the IAP family. Furthermore, the survival function of the phosphotidylinositol-3' kinase (PI3K)/AKT- and NF-kappaB-pathways are illustrated. A detailed molecular knowledge of the anti-apoptotic mechanisms of PDAC cells will help to improve therapies for this dismal disease and therapeutic strategies targeting the programmed cell death machinery are in early preclinical and clinical development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / physiology*
  • Carcinoma, Pancreatic Ductal / drug therapy
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Cell Death
  • Humans
  • Inhibitor of Apoptosis Proteins / pharmacology
  • Models, Biological
  • Oncogene Protein v-akt / metabolism
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Death Domain / antagonists & inhibitors
  • Receptors, Death Domain / metabolism
  • Signal Transduction*

Substances

  • Inhibitor of Apoptosis Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Death Domain
  • Phosphatidylinositol 3-Kinases
  • Oncogene Protein v-akt