Indeed, functional depletion of DDR effectors WDHD1, DSCC1, CSNK2B, POLR2I, and RAD54L in HNSCC cells treated with cisplatin results in decreased ATR serine/threonine kinase (ATR) phosphorylation and reduces cisplatin-induction of γ H2AX foci, suggesting that impaired DDR signaling is a driving mechanism of cisplatin resistance in HNSCC in vitro (21). This evidence concerns the gene H2AX and head and neck squamous cell carcinoma.