TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells

Susann Voigt, Stephan Philipp, Parvin Davarnia, Supandi Winoto-Morbach, Christian Röder, Christoph Arenz, Anna Trauzold, Dieter Kabelitz, Stefan Schütze, Holger Kalthoff, Dieter Adam

The cytokine TRAIL represents one of the most promising candidates for the apoptotic elimination of tumor cells, either alone or in combination therapies. However, its efficacy is often limited by intrinsic or acquired resistance of tumor cells to apoptosis. Programmed necrosis is an alternative, molecularly distinct mode of programmed cell death that is elicited by TRAIL under conditions when the classical apoptosis machinery fails or is actively inhibited. The potential of TRAIL-induced programmed necrosis in tumor therapy is, however, almost completely uncharacterized. We therefore investigated its impact on a panel of tumor cell lines of wide-ranging origin.