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Epigenetics and DNA Methylation / Cancer Cells and Metastasis / Cancer, Hypoxia, and Metabolism · Journal article
Febs Letters · August 15, 2026
Raises a question worth testing. It does not answer one.
This is a narrative review of the epigenetic mechanisms underlying cancer lineage plasticity, including chromatin remodeling, histone modifications, DNA methylation, and noncoding RNA activity. The authors propose that epigenetic deregulation drives lineage switching and therapy resistance, and suggest therapeutic opportunities in targeting the epigenome; however, no primary empirical data or clinical trial results are reported.
Journal article.
Lineage plasticity is driven by nonmutational epigenetic mechanisms including chromatin accessibility shifts, histone modifications, DNA methylation, and noncoding RNA activity Cancer-cell plasticity extends beyond epithelial-mesenchymal plasticity to dedifferentiation, transdifferentiation into neuroendocrine or squamous lineages, and stem cell-like reprogramming Polycomb and Trithorax complexes, chromatin modifier activity, and enhancer reprogramming affect lineage identity and enable multi-lineage plasticity
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
This is a narrative review synthesizing mechanistic concepts about epigenetic drivers of cancer cell plasticity, raising questions about therapeutic targets rather than reporting primary empirical data or clinical outcomes.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
Lineage plasticity develops as tumor cells overcome terminal differentiation barriers, adapt to environmental stressors, and acquire metastatic, therapy-resistant phenotypes. These phenotypic transitions are driven by nonmutational epigenetic mechanisms, including dynamic shifts in chromatin accessibility, histone modifications, DNA methylation, and noncoding RNA activity beyond genetic alterations. While epithelial-mesenchymal plasticity (EMP) remains a foundational model, cancer-cell plasticity extends into a broader pan-plasticity spectrum encompassing dedifferentiation, transdifferentiation into neuroendocrine or squamous lineages, and stem cell-like reprogramming. In this review, we evaluate how the antagonistic interplay between Polycomb and Trithorax complexes, chromatin modifier activity, and enhancer reprogramming affects lineage identity and enables multi-lineage plasticity in cancer. We further discuss extrinsic mechanisms reinforced by the tumor microenvironment, particularly hypoxia, chronic inflammation, and metabolic stress, that rewire the epigenetic landscape to stabilize plastic states. Collectively, these data underscore epigenetic deregulation as a primary driver of lineage plasticity and intratumoral heterogeneity, while revealing therapeutic vulnerabilities and the potential to reverse plasticity and overcome therapy resistance by targeting the epigenome.
Taken from the source record, never inferred. Follow any of these and new work involving them reaches your briefing.