These mediators include chromatin-modifying enzymes (histone deacetylases (HDACs)) [208], histone demethylases KDM6A/B [181], signaling pathways (Wnt) [146], IL6-STAT3 [209,210], etc. Since TME is also a critical regulator of cellular plasticity, targeting the TME-derived components along with the cancer cells is an attractive strategy to combat the cancer plasticity [197,211,212]. The gene discussed is STAT3; the disease is cancer.