NF-κB as a target for pancreatic cancer therapy.

Abstract

INTRODUCTION:

Pancreatic cancer is the fourth leading cause of adult cancer mortality in the USA. It represents one of the greatest challenges in cancer treatment. The NF-κB transcriptional factors are constitutively activated in the majority of pancreatic cancers and are involved in the regulation of numerous aspects of tumor development and progression. NF-κB and the signaling cascades that regulate its activity have thus become attractive targets for novel therapeutic approaches for pancreatic cancer.

AREAS COVERED:

This review describes and discusses the most important advances in the comprehension of the complex molecular biology of NF-κB, as well as the development of novel NF-κB-targeting strategies for the treatment of pancreatic cancer.

EXPERT OPINION:

Although the inhibition of NF-κB, especially when combined with more classic chemotherapeutic drugs, could be a promising therapeutic strategy, direct targeting NF-κB still faces important challenges. In the future, targeting nonredundant cytosolic mediators of the activation of NF-κB - such as TNF receptor associated factor family member-associated NF-κB activator -binding kinase 1 (TBK1) and TGF-beta activated kinase 1 (TAK1) - could represent a better approach to inhibit key processes in pancreatic tumor cells and make a difference for this devastating disease.

• Authors: Carmine Carbone, Davide Melisi
• Journal: Expert opinion on therapeutic targets (Expert Opin Ther Targets) Vol. 16 Suppl 2 Pg. S1-10 (Apr 2012) ISSN: 1744-7631 [Electronic] England
• PMID: 22443181 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• KRAS protein, human
• NF-kappa B
• Proto-Oncogene Proteins
• MAP Kinase Kinase Kinases
• Proto-Oncogene Proteins p21(ras)
• ras Proteins

Topics

• Animals
• Humans
• MAP Kinase Kinase Kinases (metabolism)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Pancreatic Neoplasms (drug therapy, metabolism)
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins p21(ras)
• ras Proteins (metabolism)