At the mechanistic level, BRD4, NF-κB p65, and Mediator complexes collaborate to form SEs at regions of stemness-associated genes, such as TP63, FOSL1, and MET. Disruptive interventions targeting SEs, such as bromodomain and extra terminal domain inhibitors (BETis) or the CRISPR interference strategy, effectively inhibit CSC self-renewal and ablate CSC populations, ultimately hindering invasive growth and lymph node metastasis in HNSCC [18]. Here, FOSL1 is linked to head and neck squamous cell carcinoma.