NF-κB as a target for pancreatic cancer therapy

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.

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.

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.