Sequential transcriptional waves and NF-κB-driven chromatin remodeling direct drug-induced dedifferentiation in cancer - PubMed
4 hours ago
- #Chromatin Remodeling
- #Drug Resistance
- #NF-kappaB
- Drug-induced dedifferentiation into drug-tolerant persister states is a key cancer escape mechanism, limiting therapy durability.
- Study uses high-resolution multi-omics and modeling in BRAF-mutant melanoma, revealing a hysteretic transition with two transcriptional waves driving chromatin reconfiguration.
- NF-κB/RelA-mediated chromatin remodeling is identified as central to dedifferentiation, validated via RelA-target gene modulation and an epigenome plasticity gauge.
- Oxidative stress-activated NF-κB/RelA is a common driver across cancer models, linking stress to drug tolerance and progression.