Therapeutic Targeting of Apoptotic Pathways: Novel Aspects in Pancreatic Cancer

A.      Neesse; T.M.      Gress; P.      Michl

Abstract

Pancreatic cancer constitutes one of the most aggressive tumours with a 5-year survival rate of less than 5%. It is characterized by a high degree of resistance to apoptosis which is associated by high expression levels of multiple prosurvival proteins of the extrinsic and intrinsic apoptosis signalling cascades. This review focuses on current knowledge of apoptotic pathways involved in pancreatic cancer and mechanisms of resistance to apoptosis, including alterations in the death receptor and mitochondrial pathways, as well as anti-apoptotic effects of NF-kB and Akt signalling and the impact of histon-modifying enzymes such as histondeacetylases (HDAC). Furthermore, the therapeutic implications of modulating pro-survival pathways by specific inhibitors investigated in preclinical and clinical trials will be discussed.

Keywords: Pancreatic cancer, apoptosis, therapeutic targets, extrinsic pathway, intrinsic pathway, HDAC, NF-kB, Akt, tumor stroma, apoptosis, pancreatic cancer, mechanisms of resistance