Emerging evidence highlights that epigenetic alterations—including DNA methylation, histone modification, and chromatin remodeling—play a pivotal role in mediating both intrinsic and acquired resistance to hormone therapies. These epigenetic changes can lead to the silencing of hormone receptor genes, activation of alternative signaling pathways, and reprogramming of cellular states, all of which contribute to tumor cells’ ability to evade the effects of therapy and persist despite treatment. Understanding and targeting these epigenetic mechanisms has therefore become a key area of investigation in the quest to overcome hormone therapy resistance and improve patient outcomes.

Epigenome editing technologies, such as CRISPR/dCas9-based systems, have unlocked new possibilities for precisely reprogramming epigenetic marks at specific genomic loci. These tools offer unprecedented opportunities to reverse abnormal epigenetic states, restore hormone sensitivity, and potentially overcome therapy resistance. In addition to advancing fundamental understanding of the molecular underpinnings of resistance, these innovative strategies may lead to the development of next-generation personalized therapeutics.

This Research Topic aims to bring together cutting-edge original research, reviews, and perspectives focused on epigenome editing as a strategy to address hormone therapy resistance in breast cancer. We welcome submissions in, but not limited to, the following areas:

•Mechanistic studies elucidating the epigenetic basis of hormone therapy resistance in breast cancer
•Preclinical or translational research applying precise epigenome editing technologies to restore hormone sensitivity
•Development and optimization of novel epigenome editing tools and delivery systems
•Integration of multi-omics data to identify candidate epigenetic targets for therapy
•Challenges and advances in targeted delivery of epigenome editors to breast tumors
•Biomarker discovery for predicting and monitoring response to epigenome editing interventions
•Ethical, regulatory, and clinical considerations for the therapeutic application of epigenome editing in breast cancer

By shedding light on the therapeutic promise and ongoing hurdles of epigenome editing in this context, this collection aims to accelerate progress toward more effective and durable treatments for patients with hormone therapy–resistant breast cancer.

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Epigenome Editing to Overcome Hormone Therapy Resistance in Breast Cancer