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Efficacy of a triple treatment with irradiation, agonistic TRAIL receptor antibodies and EGFR blockade

Item Type:Article
Title:Efficacy of a triple treatment with irradiation, agonistic TRAIL receptor antibodies and EGFR blockade
Creators Name:Niyazi, M. and Marini, P. and Daniel, P.T. and Humphreys, R. and Jendrossek, V. and Belka, C.
Abstract:BACKGROUND AND PURPOSE: : Since the efficacy of a single targeted agent in combination with ionizing radiation is limited by putative treatment resistances, a rationally designed triple treatment consisting of an agonistic antibody targeting either TRAIL-R1 (mapatumumab) or TRAIL-R2 (lexatumumab), radiation and an epidermal growth factor receptor-(EGFR-)inhibiting antibody (cetuximab) was tested. MATERIAL AND METHODS: : Induction of apoptosis after triple treatment was determined in Colo205, HCT116 and FaDu cells by Hoechst 33342 stain. The degree of interaction was determined by isobologram analysis. A knockout variant of HCT116 was used to examine Bax dependence of the triple treatment. The role of Akt/PKB signaling was analyzed using the phosphatidylinositol 3-kinase inhibitor LY294002. Clonogenic assays were performed to examine the effect on clonogenic survival of tumor cells. RESULTS: : A synergistic effect of radiation, cetuximab and agonistic TRAIL-R antibodies was demonstrated in cell lines derived from colorectal tumors or head-and-neck cancers. The efficacy of this multimodal approach was dependent on Bax and inhibition of Akt/PKB in the cell systems used. The results also show a positive impact on clonogenic cell death in several cell lines. CONCLUSION: : These data suggest that rationally designed multimodal therapy approaches integrating radiation with more than one targeted agent will open new perspectives in radiation oncology.
Keywords:Radiotherapy, TRAIL Antibodies, Mapatumumab, Lexatumumab, Cetuximab, Triple Treatment
Source:Strahlentherapie und Onkologie
Publisher:Urban & Vogel
Page Range:8-18
Date:January 2009
Official Publication:https://doi.org/10.1007/s00066-009-1856-4
PubMed:View item in PubMed

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