Epigenetic regulation of cancer stem cell plasticity and relapse competence in EGFR-mutant lung cancer
Year: 2026
Type: review
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.
Source: Frontiers in Oncology
Authors: Xiangxiang Sun, Shengshan Xu, Qian Guo
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7222939066