Glycogen synthase kinase-3 beta; a new target in pancreatic cancer?

ABSTRACT

Glycogen synthase kinase (GSK) was initially described as a key enzyme involved in glycogen metabolism. However, since that time it has been found to regulate a diverse range of cell functions. In addition to having a major role in the regulation of the important onco-protein beta-catenin, GSK is also a critical regulator of NF-kappaB. NF-kappaB comprises a family of transcription factors which activate the expression of a wide array of genes involved in inflammation, tumourigenesis, metastasis, differentiation, embryonic development, apoptosis. Inflammation mediated by the NF-kappaB family has been implicated in the initiation of pancreatic cancer, resistance to chemotherapy and the development of the debilitating cancer cachexia seen with advanced disease. Hence, GSK has potential as an important new target both in the treatment of resectable pancreatic cancer as an adjuvant to surgery, and in the palliation of inoperable tumours.