Molecular Pathways: The Necrosome-A Target for Cancer Therapy

Publikation: Beitrag in FachzeitschriftÜbersichtsartikel (Review)BeigetragenBegutachtung


Necroptosis is a caspase-8-independent cell death that requires coactivation of receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3) kinases. The necrosome is a complex consisting of RIP1, RIP3, and Fas-associated protein with death domain leading to activation of the pseudokinase mixed lineage kinase like followed by a rapid plasma membrane rupture and inflammatory response through the release of damage-associated molecular patterns and cytokines. The necrosome has been shown to be relevant in multiple tumor types, including pancreatic adenocarcinoma, melanoma, and several hematologic 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. Clin Cancer Res; 23(5); 1132-6. ©2016 AACR.


Seiten (von - bis)1132-1136
FachzeitschriftClinical cancer research : an official journal of the American Association for Cancer Research
PublikationsstatusVeröffentlicht - 1 März 2017

Externe IDs

PubMedCentral PMC5334358
Scopus 85014699910


Ziele für nachhaltige Entwicklung


  • Apoptosis/drug effects, Cell Lineage/drug effects, Humans, Molecular Targeted Therapy, Multiprotein Complexes/drug effects, Necrosis/genetics, Neoplasms/drug therapy, Nuclear Pore Complex Proteins/antagonists & inhibitors, RNA-Binding Proteins/antagonists & inhibitors, Receptor-Interacting Protein Serine-Threonine Kinases/antagonists & inhibitors, Tumor Microenvironment/drug effects