Primers on molecular pathways. The glycogen synthase kinase-3beta.

Despite tremendous scientific effort, conventional treatment approaches have had little impact on the course of pancreatic ductal adenocarcinoma. Therefore, urgency is needed to understand the molecular mechanisms underlying the development of pancreatic cancer with the hope that this will lead to preventative and treatment strategies to improve the outcome of the disease. Numerous factors contribute to progression of this disease, including constitutively active NF kappa B, which has been shown to positively influence cancer cell survival, proliferation, invasion, metastasis and chemoresistance. Recently, the cytoplasmic serine/threonine protein kinase glycogen synthase kinase-3beta (GSK-3beta) was found to regulate NF kappa B activation and the proliferation and survival of pancreatic cancer cells. Moreover, recent studies in other human malignancies have implicated GSK-3beta as a regulator of cancer cell proliferation, survival and chemoresistance through distinct mechanisms. Thus, GSK-3beta has emerged as a viable therapeutic target in the treatment of several human neoplasms. (c) 2007 S. Karger AG, Basel and IAP.