Epigenetic Editing to Overcome Therapy Resistance in Human Cancer

Therapy resistance remains one of the most formidable challenges in oncology. Despite significant advances in targeted therapies, immunotherapies, and chemotherapy regimens, a substantial proportion of patients experience disease relapse driven by resistant cell populations. Emerging evidence positions the epigenome as a central mediator of this resistance, with cancer cells exploiting chromatin remodelling, aberrant DNA methylation, and dysregulated histone modifications to evade treatment pressure and sustain proliferative survival.Epigenetic editing offers a transformative approach to address this problem. Unlike conventional epigenetic drugs that act broadly across the genome, programmable epigenetic tools such as dCas9 fused to catalytic effector domains can rewrite chromatin states at specific loci with unprecedented precision. This allows researchers to silence oncogenic programs, reactivate silenced tumour suppressors, and reverse the transcriptional rewiring that underpins acquired or intrinsic resistance phenotypes.This Research Topic aims to consolidate and advance knowledge at the intersection of epigenetic editing and cancer therapy resistance. We invite original research articles, reviews, and methods papers spanning the following areas:Mechanisms by which epigenetic dysregulation drives resistance to targeted therapy, immunotherapy, chemotherapy, and radiotherapy. Development and optimisation of CRISPR based epigenetic editors, including CRISPRa, CRISPRi, and base editing platforms applied in cancer models. Identification and functional validation of epigenetic resistance biomarkers using multi-omics and single cell approaches. Preclinical and translational studies using epigenetic editing to restore drug sensitivity in resistant tumours. Delivery strategies for epigenetic editing tools in vivo, including nanoparticle and viral vector systems. Combination strategies pairing epigenetic editors with existing standard of care therapies. Ethical, safety, and off target considerations unique to therapeutic epigenome editing in cancer.This collection will serve as a critical resource for researchers, clinicians, and translational scientists working to develop the next generation of cancer therapies that target the epigenetic plasticity underlying resistance. By bringing together mechanistic insight and therapeutic innovation, we aim to accelerate the path from bench to clinic. Topic editors: Jiatong Xiao, Kevin Ni, Zhenyu Nie Source: https://www.frontiersin.org/research-topics/82945/epigenetic-editing-to-overcome-therapy-resistance-in-human-cancer