Targeting Necroptosis in Antitumor Therapy
Necroptosis is an emerging mode of programmed cell death that is defined at the molecular level through involvement of receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL). In contrast to apoptosis, phosphorylation is a key event in necroptosis. Necroptosis can be triggered in response to various cell-surface receptors, such as death receptors in the tumor necrosis factor receptor family, Toll-like receptors, and interferon receptors. Because apoptotic machinery is often impaired in cancer cells, necroptosis has garnered attention as a promising strategy to treat apoptosis-resistant cancer. Moreover, since necroptosis leads to release of intracellular immunogenic contents and is therefore highly immunogenic, it has the potential to promote robust antitumor adaptive immune response. In this chapter, we describe current understanding of the role of necroptosis in cancer progression and discuss strategies through which we can harness the power of necroptosis in cancer therapy.
