Radiosensitization by erlotinib and veliparib in esophageal squamous cell cancer.

70 Background: Dysregulation of the HER/EGFR family is identified in esophageal cancers and confers resistance and inferior survival rates. In addition to their unique selectivity in killing DNA repair-deficient tumors, poly-ADP ribose polymerase inhibitors (PARPi) can enhance radiation-induced cytotoxicity. We and others have also previously demonstrated attenuation of DNA repair capacity in HER-inhibited cells to induce a contextual synthetic lethal interaction with PARPi. We thus hypothesized that erlotinib, a tyrosine kinase inhibitor directed against HER1/HER2, could induce a transient DNA repair deficit and subsequently increase DNA damage with the PARPi veliparib in esophageal cancer cells while increasing tumor radiation (RT) sensitivity. Methods: Esophageal SCC cell lines (KYSE-30, KYSE-410, and OE-21) were treated with combinations of vehicle, erlotinib, veliparib (a PARP1/2 inhibitor), and RT. DNA damage and repair and signaling proteins were assessed by immunofluorescence staining of cells for...