Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions

Abstract

Cancer remains a major therapeutic challenge owing to its complex pathogenesis and the limitations of current treatments, such as poor specificity, toxicity, and multidrug resistance. Chromatin accessibility, which is dynamically regulated by genetic, epigenetic, and environmental factors, plays crucial roles in cancer initiation and progression. However, substantial obstacles persist in developing therapeutic strategies that target chromatin accessibility and translating them into clinical practice. This review comprehensively summarizes the biological functions and regulatory mechanisms of chromatin accessibility in tumors, encompassing tumorigenesis, progression, metabolic reprogramming, angiogenesis, stemness, tumor immune microenvironment, and therapy resistance. We integrate comparisons between human and murine models and detail key profiling technologies, including Assay for Transposase‑Accessible Chromatin with high‑throughput sequencing, DNase‑seq, single‑cell multiomics, and three-dimensional chromatin‑conformation assays. Furthermore, we compile recent preclinical and clinical trials that utilize chromatin accessibility as a biomarker or therapeutic target, along with combination strategies involving chemotherapy, immunotherapy, targeted therapy, and radiotherapy. From a multiomics and interdisciplinary perspective, we discuss current limitations in translating fundamental research into clinical applications and highlight future directions for epigenetics‑based precision oncology.

Keywords

cancer / chromatin accessibility / epigenetic regulation / therapeutic strategies

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