Epigenetic mechanisms in disseminated tumor cell dormancy and reactivation: A scoping review
Year: 2026
Type: article
Abstract: Disseminated tumor cells (DTCs) can lie dormant before reactivating to cause metastatic relapse, yet the epigenetic mechanisms driving these transitions are not fully understood. This scoping review identifies epigenetic mechanisms linked to DTC dormancy and reactivation in solid malignancies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, we searched PubMed, Embase, and Web of Science for studies published from January 2016 to August 2026. Two independent reviewers screened records and extracted data for descriptive and narrative synthesis. Out of 104 unique records, 14 studies were included, with 12 (85.7%) focusing on breast or prostate cancer. We identified four mechanistic categories: histone modifications and variants, DNA methylation, chromatin remodeling and enhancer reprogramming, and non-coding RNAs. These mechanisms were associated with cell-cycle arrest, transcriptional repression, stemness, and immune interactions. Nuclear Receptor Subfamily 2 Group F Member 1 (NR2F1) was the most frequently reported molecular node, appearing in 6 of 14 studies, although functional evidence varied. Chromatin bookmarking and enhancer-based transcriptional memory were also implicated in maintaining dormancy. The evidence was predominantly preclinical, including two preprints and two conference abstracts, and lacked prospective clinical validation. Reactivation-specific mechanisms and immune interactions remain underexplored. These findings map interconnected epigenetic programs influencing DTC fate and highlight crucial areas for mechanistic and clinical validation to inform strategies for preventing metastatic relapse.
Source: Biomolecules and Biomedicine
Institution: Nova Southeastern University
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7134099667