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

Area of Science:

• Oncology
• Epigenetics
• Genomics

Background:

• Cancer poses significant therapeutic challenges due to complexity and treatment limitations like resistance and toxicity.
• Chromatin accessibility, influenced by various factors, is critical in cancer initiation and progression.
• Developing effective therapies targeting chromatin accessibility remains a significant hurdle for clinical application.

Purpose of the Study:

• To comprehensively review the biological roles and regulatory mechanisms of chromatin accessibility in tumors.
• To detail key profiling technologies for assessing chromatin accessibility.
• To summarize current clinical trials and combination strategies involving chromatin accessibility, and discuss future directions for epigenetics-based precision oncology.

Main Methods:

• Review of biological functions and regulatory mechanisms of chromatin accessibility in cancer.
• Integration of human and murine model comparisons.
• Detailed examination of profiling technologies: Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq), DNase-seq, single-cell multiomics, and 3D chromatin conformation assays.
• Compilation of preclinical and clinical trials and combination strategies.

Main Results:

• Chromatin accessibility influences tumorigenesis, progression, metabolic reprogramming, angiogenesis, stemness, the tumor immune microenvironment, and therapy resistance.
• Key technologies like ATAC-seq and DNase-seq enable detailed profiling.
• Numerous trials explore chromatin accessibility as a biomarker and therapeutic target, with promising combination strategies.

Conclusions:

• Chromatin accessibility is a pivotal factor in cancer biology and a promising target for novel therapies.
• Significant progress has been made in profiling and targeting chromatin accessibility, with ongoing clinical investigations.
• Overcoming challenges in translating research findings is crucial for advancing epigenetics-based precision oncology.