Volume 2, Issue 3, Pages (March 2015)

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Volume 2, Issue 3, Pages 264-271 (March 2015) Clinical Translation and Validation of a Predictive Biomarker for Patritumab, an Anti- human Epidermal Growth Factor Receptor 3 (HER3) Monoclonal Antibody, in Patients With Advanced Non-small Cell Lung Cancer Jeanne Mendell, Daniel J. Freeman, Wenqin Feng, Thore Hettmann, Matthias Schneider, Sabine Blum, Jens Ruhe, Johannes Bange, Kenji Nakamaru, Shuquan Chen, Zenta Tsuchihashi, Joachim von Pawel, Catherine Copigneaux, Robert A. Beckman EBioMedicine Volume 2, Issue 3, Pages 264-271 (March 2015) DOI: 10.1016/j.ebiom.2015.02.005 Copyright © 2015 The Authors Terms and Conditions

Fig. 1 Patritumab and HER3 signaling pathway. (A) Binding of the ligand heregulin to HER3 induces a conformational change that allows for receptor dimerization of HER3 with HER family receptors, such as EGFR or HER2. (B) Heterodimerization initiates the transphosphorylation of HER3 at specific tyrosine residues by the kinase of its heterodimeric partner. (C) The phosphorylated tyrosine kinase residues create 6 direct docking sites for PI3K, leading to the activation of other molecules further downstream in the PI3K–Akt pathway. EGFR: epidermal growth factor receptor; HER: human epidermal growth factor receptor; PI3K: phosphatidylinositol-3-kinase. EBioMedicine 2015 2, 264-271DOI: (10.1016/j.ebiom.2015.02.005) Copyright © 2015 The Authors Terms and Conditions

Fig. 2 Distribution of HRG mRNA in the HERALD study. ΔCt: median delta threshold cycle; Q: quartile. EBioMedicine 2015 2, 264-271DOI: (10.1016/j.ebiom.2015.02.005) Copyright © 2015 The Authors Terms and Conditions

Fig. 3 Progression-free survival in HRG-high and HRG-low patients in placebo and patritumab arms. HRG: heregulin. EBioMedicine 2015 2, 264-271DOI: (10.1016/j.ebiom.2015.02.005) Copyright © 2015 The Authors Terms and Conditions

Fig. 4 Distribution of HRG mRNA in non-small cell lung cancer samples. ΔCt: median delta threshold cycle; Q: quartile. EBioMedicine 2015 2, 264-271DOI: (10.1016/j.ebiom.2015.02.005) Copyright © 2015 The Authors Terms and Conditions