Epigenetic Mechanisms Underlying Therapy Resistance in Cancer Stem Cells

Cancer biology increasingly recognizes that cancer stem cells (CSCs) represent a critical subpopulation within tumors, marked by their self-renewal, differentiation, and inherent resistance to standard treatments. This resistance plays a central role in cancer persistence, metastasis, recurrence, and overall poor patient prognosis. Recent studies have underscored the significance of epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, in maintaining CSC properties and regulating gene expression networks that underpin stemness and evasive behavior. Beyond chromatin-focused processes, dynamic RNA epigenetic modifications such as m6A, m5C, ac4C, and m7G have been shown to further control transcript fate and cell identity. Despite mounting evidence linking these intricate epigenetic changes to therapy resistance and tumor progression, significant knowledge gaps remain regarding their exact molecular crosstalk, interplay with metabolic and immune pathways, and actionable vulnerabilities.This Research Topic aims to advance the understanding of how epigenetic regulation controls CSC biology and contributes to therapy resistance. We seek to clarify the key processes through which DNA and RNA modifications modulate CSC behavior, highlighting not only fundamental mechanistic discoveries but also their translational relevance for cancer therapy. By integrating comprehensive mechanistic and bioinformatics analyses, experimental data, and translational perspectives, this initiative seeks to map out the molecular landscape driving CSC resilience. Ultimately, the goal is to generate actionable knowledge that identifies novel biomarkers and therapeutic strategies, thereby addressing one of the major obstacles in current oncology: the eradication of refractory CSC-driven disease.The scope of this Research Topic encompasses multidisciplinary investigations into the epigenetic mechanisms orchestrating CSC phenotype and therapy resistance, while focusing on their implications for clinical intervention and patient outcome. Manuscripts should be rooted in rigorous experimental evidence or in-depth analyses and can span basic, translational, or computational research. To drive forward the field, we welcome studies on the following themes:- DNA methylation, histone modifications, chromatin remodeling, non-coding RNAs, and RNA marks (m6A, m5C, ac4C, m7G) in CSC regulation.- Mechanisms of CSC-driven drug resistance, tumor relapse, and failure of existing therapies.- The contribution of CSC epigenetics to metastasis, tumor heterogeneity, and metabolic reprogramming.- Identification and characterization of CSC molecular markers and their relevance as prognostic or predictive biomarkers.- Utilization of single-cell technologies to dissect CSC heterogeneity and lineage-specific epigenetic programs.- Discovery and mechanistic analysis of therapeutic strategies aimed at targeting CSC epigenetic pathways.- Insights into CSC-mediated immune evasion, alterations of the tumor immune environment, and modulation of immunotherapy response.Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases that are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of the scope of this Research Topic. Topic editors: Xiulin Jiang, Christine Zhang Source: https://www.frontiersin.org/research-topics/78765/epigenetic-mechanisms-underlying-therapy-resistance-in-cancer-stem-cells