Fig. 2.

Schematic overview on the relationship of cancer and necroptosis as friend or foe. Events listed under “friend?” are beneficial for the survival of the whole tumor (e.g., induction of neovascularization) or for the survival of the individual cancer cell itself (e.g., downregulation/lack of key components of necroptosis). The induction of autophagy can further improve the invasion efficacy of metastatic cells by strengthening their fitness against necroptosis. Compounds that induce necroptosis in cancer cells or at least sensitize them for necroptosis are listed under “foe?”. In addition to those chemicals and naturally occurring substances, viral anti-apoptotic proteins (e.g., M45) and nanoparticles (e.g., ZnO and Ag) have also been shown to induce necroptosis in cancer cells. Since the sphingolipid ceramide has been reported as a key downstream mediator of necroptosis, the manipulation of intracellular sphingolipid levels may also represent a feasible target to induce necroptosis in cancer cells. The promotion of inflammatory responses by necroptosis may either be beneficial for the tumor (e.g., by promoting cancer cell spreading), or may contribute to a more efficient clearance of tumor cells by the immune system via the release of cytokines and DAMPs