TY - JOUR T1 - DNA Double-strand Break Signaling Is a Therapeutic Target in Head and Neck Cancer JF - Anticancer Research JO - Anticancer Res SP - 5393 LP - 5403 DO - 10.21873/anticanres.15351 VL - 41 IS - 11 AU - JIANCHUN WU AU - KATE JILLIAN GALVAN AU - RYAN D. BOGARD AU - CARYN E. PETERSON AU - ARDAMAN SHERGILL AU - DAVID L. CROWE Y1 - 2021/11/01 UR - http://ar.iiarjournals.org/content/41/11/5393.abstract N2 - Background: Head and neck cancer (HNC) is common worldwide. Given poor outcomes for patients with HNC, research into targeted therapies is needed. Ataxia telangiectasia mutated (ATM) is a DNA damage kinase which is activated by double-strand DNA breaks. We tested the effects of a novel ATM inhibitor on HNC cell lines and xenografts. Materials and Methods: p53-Binding protein 1 and phosphorylated ATM were localized in cultured cells by immunofluorescence microscopy. Protein expression was determined by western blot. Tumor xenografts were established by injecting HNC lines into immunocompromised mice. Tumor sections were characterized by immunohistochemistry. Apoptotic cells were determined by terminal transferase-mediated dUTP nick-end labeling assay. Results: ATM inhibition increased double-strand DNA breaks at replication foci in HNC cell lines. ATM inhibition affected cell-cycle regulatory protein expression, blocked cell-cycle progression at the G2/M phase and resulted in apoptosis. Conclusion: ATM inhibition may be therapeutically useful in treating HNC. ER -