Recent Patents Concerning Targeted Therapy of Apoptosis Resistance in Pancreatic Cancer
Kristin Werner, Felix Ruckert, Hans-Detlev Saeger, Robert Grutzmann and Christian Pilarsky
Affiliation: Department of Visceral, Thoracic and Vascular Surgery, University Hospital Dresden, Fetscherstrasse 74 DE-01307 Dresden (Germany).
Keywords: Apoptosis, caspase, IAPs, pancreatic cancer, patents, PDAC, targeted therapy, Programmed cell death, Nuclear Lamin, Tumor necrosis factor, Apoptosome protein complex, mitochondrial amplification loop, post-mitochondrial signal transduction
Pancreatic cancer is one of the most malignant forms of cancer. Due to numerous defects of the apoptosis machinery this tumor shows a high resistance towards conventional oncological therapies.
On the level of the extrinsic pathway, signal transduction is flawed by over-expression of decoy receptors but also by a dysfunctional death inducing signaling complex (DISC). The mitochondrial pathway, normally stimulated by cell stress and toxic agents is impeded by over-expression of anti-apoptotic members of the Bcl-2 protein family and the so-called inhibitor of apoptosis proteins (IAPs).
To overcome the dysfunction of the apoptosis pathway, new therapeutics focus on molecular targets within the apoptosis pathway. Recently, many new treatment modalities have been reported like recombinant ligands of the cell death receptors or inhibitors of anti-apoptotic Bcl-2 members. Furthermore, various substances for the direct activation of the caspase cascade were patented and the over-expression of IAPs could be treated by binding inhibitors or using RNA interference techniques. The present review aims at giving an overview on these new treatment modalities.
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