Genes encoding key epigenetic regulators, including Lysine Demethylase 6A (KDM6A), are frequently mutated in bladder cancer. Here, the authors show that loss of KDM6A promotes formation of extrachromosomal circular DNA (eccDNA), genomic instability, and metabolic reprogramming, driving resistance to cisplatin chemotherapy while simultaneously enhancing sensitivity to immune checkpoint inhibitors.
- Pratishtha Singh
- Ranit D’Rozario
- Sangeeta Goswami