The roles of Hedgehog signalling and NF-κB activity in pancreatic cancer and opportunities for treatment

Abstract

Pancreatic cancer is the seventh most common form of cancer-related death in the world, affecting hundreds of thousands of people worldwide every year. Treatment for this type of cancer is largely ineffective and future treatments are likely to involve targeting signalling pathways involved in the proliferation of pluripotent stem cells. There are a variety of signalling pathways involved in the pathogenesis of the disease, including Hedgehog (Hh) and nuclear factor-kappaB (NF-κB). Overexpression of Hh ligands or alterations in other areas of the Hh signalling pathway may lead to tumour formation. Inhibition of Hh ligands, Smoothened or Gli proteins, or up-regulation of Patched expression, could form the basis of new treatments. NF-κB is often active in pancreatic cancer cells and down-regulation of NF-κB activating molecules can inhibit tumour progression in cell culture studies. Clinical trials show some promising results in novel drugs. There is growing evidence to suggest the interaction between these two signalling pathways. NF-κB appears to play a role upstream of the Hh pathway. This article looks at the roles these pathways play in pancreatic cancer and explores current research into targeting them for treatment.