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Model of ENb-TRAIL function. EGFR and DR5 are co-engaged at the surface of tumor cells. Trimerized ENb-TRAIL binds simultaneously to EGFR and DR5 leading to receptor clustering and amplification of apoptotic signal. Blocking EGFR with Cetuximab or ENb abolishes ENb-TRAIL binding to EGFR and subsequent activation of apoptosis. EGFR tyrosine kinase inhibitor, Erlotinib inhibits EGFR and AKT activity but does not influence activation of apoptosis by ENb-TRAIL.
