Epigenetic regulation of cancer stem cell plasticity and relapse competence in EGFR-mutant lung cancer
- 1Jiaxing First Hospital
- 2Department of Thoracic Surgery, Jiangmen Central Hospital
- 3Zhongnan Hospital of Wuhan University
Abstract
Cancer stem cell (CSC) plasticity is increasingly linked to therapy resistance, yet CSC identity is still often inferred from persistence, stemness markers, or short-term regenerative assays. EGFR-mutant non–small-cell lung cancer is a useful setting in which to examine this problem because residual states can be sampled before stable resistance is established. Here, we focus on how chromatin remodeling, DNA methylation, histone regulation, RNA epigenetics, adaptive signaling, metabolism, and the immune microenvironment influence stem-like behavior during EGFR-targeted therapy. We assess the literature using four evidence levels: state association, functional enrichment, post-treatment durability, and lineage-resolved acquisition of durable CSC function. The available data strongly support epigenetic regulation of therapy-persistent and resistant states, and several models show functional overlap with CSC-associated phenotypes. What remains largely missing is direct evidence that a prospectively identified persister lineage later acquires serially propagating CSC function. Minimal residual disease may therefore represent a period in which relapse-competent states are present but not yet irreversibly established.
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BibTeX
@article{sun2026epigenetic,
title = {{Epigenetic regulation of cancer stem cell plasticity and relapse competence in EGFR-mutant lung cancer}},
author = {Xiangxiang Sun and Shengshan Xu and Qian Guo},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1981354},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1981354/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Epigenetic regulation of cancer stem cell plasticity and relapse competence in EGFR-mutant lung cancer
AU - Xiangxiang Sun
AU - Shengshan Xu
AU - Qian Guo
PY - 2026
DA - 2026/10/19
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1981354
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1981354/full
AB - Cancer stem cell (CSC) plasticity is increasingly linked to therapy resistance, yet CSC identity is still often inferred from persistence, stemness markers, or short-term regenerative assays. EGFR-mutant non–small-cell lung cancer is a useful setting in which to examine this problem because residual states can be sampled before stable resistance is established. Here, we focus on how chromatin remodeling, DNA methylation, histone regulation, RNA epigenetics, adaptive signaling, metabolism, and the immune microenvironment influence stem-like behavior during EGFR-targeted therapy. We assess the literature using four evidence levels: state association, functional enrichment, post-treatment durability, and lineage-resolved acquisition of durable CSC function. The available data strongly support epigenetic regulation of therapy-persistent and resistant states, and several models show functional overlap with CSC-associated phenotypes. What remains largely missing is direct evidence that a prospectively identified persister lineage later acquires serially propagating CSC function. Minimal residual disease may therefore represent a period in which relapse-competent states are present but not yet irreversibly established.
SN - 2234-943X
ER -