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Updated: Mar 10, 2026
Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Relevance of necroptosis in cancer
Najoua Lalaoui1,2, Gabriela Brumatti1,2
1Division of Cell Signalling and Cell Death, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Abstract:
Resistance to caspase-dependent apoptosis is often responsible for treatment failures in cancer. Finding novel therapeutic strategies that can activate alternative cell death programs appears to be appealing. Necroptosis is a form of programmed necrosis that occurs under caspase-deficient conditions. This alternative form of cell death has recently emerged as a potential anticancer therapy that could overcome apoptosis resistance. A growing understanding of the molecular events triggering necroptosis helped to examine its implication in cancer development and to define new therapeutic strategies. Genetic and proteomic analysis suggest that necroptosis is deregulated in many cancers. Various preclinical and clinical compounds induced necroptosis and have demonstrated significant therapeutic efficacy. Moreover, accumulating evidence has shown that necroptosis promotes anticancer immune response. A better knowledge of the cascade of events regulating necroptosis is expected to assess the feasibility of its therapeutic exploitation for cancer therapy.
Insights
Cancer treatment failure is linked to apoptosis resistance. Necroptosis, an alternative cell death pathway, offers a promising therapeutic strategy to overcome this resistance and enhance anticancer immunity.
Area of Science:
- Oncology
- Cell Death Research
- Immunotherapy
Background:
- Resistance to apoptosis, a programmed cell death, frequently leads to cancer treatment failure.
- Alternative cell death pathways are being explored to overcome apoptosis resistance.
- Necroptosis, a programmed necrosis, is a caspase-independent cell death mechanism.
Purpose of the Study:
- To investigate necroptosis as a potential anticancer therapeutic strategy.
- To explore the role of necroptosis in cancer development and treatment.
- To identify novel therapeutic approaches targeting necroptosis.
Main Methods:
- Review of genetic and proteomic analyses implicating necroptosis in cancer.
- Examination of preclinical and clinical studies on necroptosis-inducing compounds.
- Analysis of evidence linking necroptosis to anticancer immune responses.
Main Results:
- Necroptosis is deregulated in numerous cancer types.
- Compounds inducing necroptosis have shown significant therapeutic efficacy in preclinical and clinical settings.
- Necroptosis activation promotes an anticancer immune response.
Conclusions:
- Necroptosis represents a promising therapeutic avenue for overcoming apoptosis resistance in cancer.
- Targeting necroptosis could offer novel strategies for cancer treatment.
- Further understanding of necroptosis regulation is crucial for its clinical application.
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