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Updated: Mar 15, 2026
Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
Molecular Cell Biology of Apoptosis and Necroptosis in Cancer
Christopher P Dillon1, Douglas R Green2
1Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA. christopher.dillon@stjude.org.
Abstract:
Cell death is a major mechanism to eliminate cells in which DNA is damaged, organelles are stressed, or oncogenes are overexpressed, all events that would otherwise predispose cells to oncogenic transformation. The pathways that initiate and execute cell death are complex, genetically encoded, and subject to significant regulation. Consequently, while these pathways are often mutated in malignancy, there is considerable interest in inducing cell death in tumor cells as therapy. This chapter addresses our current understanding of molecular mechanisms contributing to two cell death pathways, apoptotic cell death and necroptosis, a regulated form of necrotic cell death. Apoptosis can be induced by a wide variety of signals, leading to protease activation that dismantles the cell. We discuss the physiological importance of each apoptosis pathway and summarize their known roles in cancer suppression and the current efforts at targeting each pathway therapeutically. The intricate mechanistic link between death receptor-mediated apoptosis and necroptosis is described, as well as the potential opportunities for utilizing necroptosis in the treatment of malignancy.
Insights
Cell death pathways like apoptosis and necroptosis eliminate damaged cells. Understanding these mechanisms offers new therapeutic strategies for targeting cancer cells.
Area of Science:
- Molecular biology
- Cellular mechanisms
- Oncology
Background:
- Cell death is crucial for eliminating damaged or stressed cells, preventing oncogenic transformation.
- Dysregulation of cell death pathways is common in cancer, making them therapeutic targets.
- Apoptosis and necroptosis are key regulated cell death pathways with complex molecular underpinnings.
Purpose of the Study:
- To review the molecular mechanisms of apoptotic cell death and necroptosis.
- To discuss the physiological roles of these pathways in cancer suppression.
- To explore therapeutic strategies targeting cell death pathways in malignancy.
Main Methods:
- Review of current literature on apoptosis and necroptosis molecular mechanisms.
- Analysis of the interplay between death receptor-mediated apoptosis and necroptosis.
- Summary of ongoing research in targeting these pathways for cancer therapy.
Main Results:
- Apoptosis involves protease activation to dismantle cells, crucial for cancer suppression.
- Necroptosis is a regulated form of necrotic cell death, mechanistically linked to apoptosis.
- Targeting these cell death pathways presents significant therapeutic opportunities in oncology.
Conclusions:
- A comprehensive understanding of apoptosis and necroptosis is vital for cancer therapy.
- Exploiting the link between apoptosis and necroptosis may yield novel anti-cancer treatments.
- Targeting cell death pathways offers a promising avenue for future cancer treatment strategies.
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