Targeting TNFR1-driven necroptosis in breast cancer
Misbahuddin Rafeeq1, Muhammad Afzal2, Muhammad Shahid Nadeem3
1Division of Basic Medical Sciences, College of Medicine, Dhofar University, Oman.
EXCLI Journal
|January 26, 2026
Summary
Tumor Necrosis Factor Receptor 1 (TNFR1) dictates breast cancer cell fate via necroptosis and other pathways. TNFR1 activation triggers epigenetic reprogramming, offering new therapeutic targets for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Tumor Necrosis Factor Receptor 1 (TNFR1) is pivotal in breast cancer cell survival, apoptosis, and necroptosis.
- TNFR1 signaling involves key pathways like NF-kB, caspase-8, and the RIPK1-RIPK3-MLKL axis.
Purpose of the Study:
- To review the role of TNFR1 in breast cancer cell death pathways, focusing on epigenetic modifications.
- To explore potential therapeutic strategies targeting the TNFR1-necroptosis axis.
Main Methods:
- Review of literature on TNFR1 signaling, necroptosis, and epigenetic regulation in breast cancer.
- Analysis of molecular mechanisms including DNA methylation, histone modification, and microRNA control.
Main Results:
- TNFR1 activation induces epigenetic changes (DNA methylation, histone modification) that reprogram cellular responses.
- The necroptotic pathway involves RIPK1-RIPK3 necrosome formation and MLKL phosphorylation.
- Biomarkers like TNFR1 expression and epigenetic markers are identified for potential therapeutic guidance.
Conclusions:
- TNFR1 signaling and necroptosis present complex therapeutic challenges due to TNF's dual role.
- Targeting the TNFR1-necroptosis pathway with epigenetic strategies and biomarker-guided therapies shows promise for breast cancer treatment.
- Further research is needed to address patient stratification and optimize therapeutic sequencing.
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