Molecular Pathways: The Necrosome-A Target for Cancer Therapy.
Molecular Pathways: The Necrosome-A Target for Cancer Therapy.
复制标题
DOI：
10.1158/1078-0432.ccr-16-0968
复制
发表时间：
2017-03-01
期刊：
影响因子：
--
通讯作者：
Miller G
中科院分区：
文献类型：
--
作者：
Seifert L;Miller G
Necroptosis is a caspase 8-independent cell death that requires co-activation of receptor-interacting protein (RIP) 1 and RIP 3 kinases. The necrosome is a complex consisting of RIP1, RIP3 and Fas-associated protein with death domain (FADD) leading to activation of the pseudokinase mixed lineage kinase like (MLKL) followed by a rapid plasma membrane rupture and inflammatory response through the release of damage-associated molecular patterns (DAMPs) and cytokines. The necrosome has been shown to be relevant in multiple tumor types, including pancreatic adenocarcinoma, melanoma and several hematological malignancies. Preclinical data suggest that targeting this complex can have differential impact on tumor progression and that the effect of necroptosis on oncogenesis is cell type- and context-dependent. The emerging data suggest that targeting the necrosome may lead to immunogenic reprogramming in the tumor microenvironment in multiple tumors and that combining therapies targeting the necrosome with either conventional chemotherapy or immunotherapy may have beneficial effects. Thus, understanding the interplay of necroptotic cell death, transformed cells, and the immune system may enable the development of novel therapeutic approaches.
