Neuregulin 1 expression is a predictive biomarker for response to AV-203, an ERBB3 inhibitory antibody, in human tumor models
作者： Kristan Meetze , Sylvie Vincent , Steven Tyler , Elizabeth K. Mazsa , Andrea R. Delpero
DOI: 10.1158/1078-0432.CCR-14-2407
关键词:
摘要: Purpose: ERBB3 is overexpressed in a broad spectrum of human cancers, and its aberrant activation associated with tumor pathogenesis therapeutic resistance to various anticancer agents. Neuregulin 1 (NRG1) the predominant ligand for can promote heterodimerization other ERBB family members, resulting multiple intracellular signaling pathways. AV-203 humanized IgG1/κ inhibitory antibody that completed first-in-human phase I clinical trial patients advanced solid tumors. The purpose this preclinical study was identify potential biomarker(s) may predict response treatment clinic. Experimental Design: We conducted vivo efficacy studies using panel xenograft models representing wide variety cancers. To biomarkers AV-203, relationship between growth inhibition (TGI) by expression levels NRG1 were evaluated these models. Results: A significant correlation observed TGI AV-203. In contrast, not correlated expression. tumors their further validated patient-derived explant Conclusions: promising biomarker cancer warrants evaluation validation as predictive Clin Cancer Res; 21(5); 1106–14. ©2014 AACR .
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