EZH2 and head and neck squamous cell carcinoma: For instance, the overexpression of EZH2, a histone methyltransferase, has been shown to stimulate chemoresistance in glioblastoma, small-cell lung cancer, and HNSCC.521,522 Regarding the underlying mechanisms, EZH2-mediated gene silencing of SLFN11, a crucial factor in DNA damage repair, via H3K27 hypermethylation, leads to chemoresistance in small-cell lung cancer cells.521 Additionally, histone methylation alterations modulate tumor cell apoptosis and proliferation to influence chemotherapy resistance.