Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells.

摘要: Approximately 30% of human breast and ovarian cancers have amplification and/or overexpression HER-2/neu gene which encodes a cell surface growth-factor receptor. Overexpression this receptor, p185HER-2/neu, is associated with poor outcome may predict clinical response to chemotherapy. Antibodies receptor cytostatic effect in suppressing growth cells p185HER-2/neu. To elicit cytocidal effect, therapy antireceptor antibody was used combination the DNA-damaging drug, cisplatin, combined treatment produced synergistic decrease growth. In addition, mediated an increased sensitivity cisplatin drug-resistant carcinoma containing multiple copies gene. evaluate mechanism for synergy, unscheduled DNA synthesis measured cancer using incorporation [3H]thymidine autoradiography, formation repair cisplatin-induced adducts also measured. Treatment led marked, dose-dependent increase significantly reduced by HER-2/neu-overexpressing cells. Therapy 35-40% reduction cisplatin-DNA after exposure and, as result, promoted drug-induced killing target This phenomenon we term receptor-enhanced chemosensitivity provide rationale more selective targeting exploitation overexpressed factor receptors cells, thus leading new strategies intervention.