EGFR blockade with ZD1839 ("Iressa") potentiates the antitumor effects of single and multiple fractions of ionizing radiation in human A431 squamous cell carcinoma

Abstract

Purpose: Signaling pathways initiated by the epidermal growth factor receptor (EGFR) play important roles in the response to ionizing radiation. In this study the consequences of inhibiting the EGFR on the response of A431 cells (human vulvar squamous cell carcinoma cells that overexpress EGFR) to radiation, were investigated in vitro and in vivo, using the selective EGFR-tyrosine kinase inhibitor, ZD1839 ("Iressa"). Methods and Materials: The effect of ZD1839 on proliferation, apoptosis, and clonogenic survival after radiation was determined in vitro. For in vivo studies, athymic nude mice with established subcutaneous A431 xenografts (∼100 mm3) were treated with either a single 10 Gy fract..