Blockade of EphB4-ephrin-B2 enhances response to EGFR inhibitor (cetuximab) and RT resulting in significant delay in tumor growth and enhanced survival in HNSCC PDX models. Tumor growth volumes are displayed in CUHN013 (A) and CUHN004 (B) tumors including cisplatin-RT treated groups in the absence and presence of sEphB4-HSA. Cisplatin-RT treated groups did not show any significant changes in tumor growth in the absence and presence of sEphB4-HSA in CUHN013 tumors. Survival graphs are shown for CUHN013 (C) and CUHN004 (D) tumors.