Academic Journal
Epigenetic heterogeneity and plasticity in therapy-induced tumor states through single-cell multi-omics.
| Title: | Epigenetic heterogeneity and plasticity in therapy-induced tumor states through single-cell multi-omics. |
|---|---|
| Authors: | Kim HJ; Ajou Energy Science Research Center, Ajou University, Suwon, Korea., Lee H; Department of Molecular Science and Technology, Ajou University, Suwon, Korea., Hong J; Department of Molecular Science and Technology, Ajou University, Suwon, Korea., Park D; Department of Molecular Science and Technology, Ajou University, Suwon, Korea.; College of Advanced Bio-Convergence Engineering, Ajou University, Suwon, Korea. |
| Source: | Molecular oncology [Mol Oncol] 2026 Oct; Vol. 20 (10), pp. 2424-2448. Date of Electronic Publication: 2026 Jun 04. |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: John Wiley & Sons, Inc Country of Publication: United States NLM ID: 101308230 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-0261 (Electronic) Linking ISSN: 15747891 NLM ISO Abbreviation: Mol Oncol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2017- : Hoboken, New Jersey : John Wiley & Sons, Inc. Original Publication: Amsterdam : Elsevier |
| MeSH Terms: | Neoplasms*/genetics , Neoplasms*/pathology , Neoplasms*/therapy , Neoplasms*/drug therapy , Single-Cell Analysis*/methods , Cell Plasticity*/genetics , Epigenesis, Genetic* , Genetic Heterogeneity*, Humans ; Multiomics ; Animals ; Epithelial-Mesenchymal Transition |
| Abstract: | Therapeutic resistance and disease recurrence remain major unresolved challenges in oncology, primarily driven by tumor heterogeneity and the inherent plasticity of cancer cells. Although multiple biological mechanisms contribute to these processes, epigenetic mechanisms are the key regulators of clonal diversification and adaptive transcriptional reprogramming under treatment pressure. This regulatory layer operates through reversible transcriptional changes that are independent of DNA sequence alterations, enabling cancer cells to respond to a selective environment. Recent advances in analytical methodologies, particularly single-cell multi-omics approaches, have markedly improved our capacity to dissect these regulatory processes at a single-cell resolution. This review explores how diverse therapeutics, including chemotherapy, targeted agents, immunotherapy, hormonal interventions, and epigenetic drugs, induce the widespread remodeling of DNA methylation patterns, histone modifications, and chromatin accessibility. These therapy-induced molecular changes drive transitions to distinct cellular states that confer survival advantages such as drug-tolerant persister (DTP) phenotypes, senescence-like populations, epithelial-mesenchymal transition (EMT) states, and immune-evasive cell populations. We further evaluated the current single-cell multi-omics platforms for profiling chromatin-based plasticity and identifying biomarkers with direct clinical relevance. Finally, we discuss how integrative multi-layer analyses enable comprehensive characterization of tumor-state evolution, providing a conceptual framework for precision oncology strategies aimed at overcoming resistance. (© 2026 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.) |
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| Grant Information: | RS-2023-00285390 National Research Foundation of Korea; RS-2024-00341899 National Research Foundation of Korea; RS-2025-23323220 National Research Foundation of Korea |
| Contributed Indexing: | Keywords: cancer epigenetics; cell state plasticity; single‐cell multi‐omics; therapeutic resistance; tumor heterogeneity |
| Entry Date(s): | Date Created: 20260604 Date Completed: 20261006 Latest Revision: 20261006 |
| Update Code: | 20261007 |
| PubMed Central ID: | PMC13398730 |
| DOI: | 10.1002/1878-0261.70285 |
| PMID: | 42237704 |
| Database: | MEDLINE |
| ISSN: | 1878-0261 |
|---|---|
| DOI: | 10.1002/1878-0261.70285 |