Anti-HER3 Domain 1 and 3 Antibodies Reduce Tumor Growth by Hindering HER2/HER3 Dimerization and AKT-Induced MDM2, XIAP, and FoxO1 Phosphorylation

Yarden, 2012, The ERBB network: at last, cancer therapy meets systems biology, Nat Rev Cancer, 12, 553, 10.1038/nrc3309 Shi, 2010, ErbB3/HER3 intracellular domain is competent to bind ATP and catalyze autophosphorylation, Proc Natl Acad Sci USA, 27, 7692, 10.1073/pnas.1002753107 Ben-Kasus, 2009, Persistent elimination of ErbB-2/HER2-overexpressing tumors using combinations of monoclonal antibodies: relevance of receptor endocytosis, Proc Natl Acad Sci USA, 106, 3294, 10.1073/pnas.0812059106 Carraway, 2010, E3 ubiquitin ligases in ErbB receptor quantity control, Semin Cell Dev Biol, 21, 936, 10.1016/j.semcdb.2010.09.006 Campbell, 2010, HER3 comes of age: new insights into its functions and role in signaling, tumor biology, and cancer therapy, Clin Cancer Res, 16, 1373, 10.1158/1078-0432.CCR-09-1218 Cook, 2011, ErbB3 ablation impairs PI3K/Akt-dependent mammary tumorigenesis, Cancer Res, 71, 3941, 10.1158/0008-5472.CAN-10-3775 Friess, 1995, Enhanced erbB-3 expression in human pancreatic cancer correlates with tumor progression, Clin Cancer Res, 1, 1413 Naidu, 1998, Expression of c-erbB3 protein in primary breast carcinomas, Br J Cancer, 78, 1385, 10.1038/bjc.1998.689 Tanner, 2006, ErbB-3 predicts survival in ovarian cancer, J Clin Oncol, 24, 4317, 10.1200/JCO.2005.04.8397 Reschke, 2008, HER3 is a determinant for poor prognosis in melanoma, Clin Cancer Res, 14, 5188, 10.1158/1078-0432.CCR-08-0186 Hayashi, 2008, High expression of HER3 is associated with a decreased survival in gastric cancer, Clin Cancer Res, 14, 7843, 10.1158/1078-0432.CCR-08-1064 Takikita, 2011, Membranous expression of HER3 is associated with a decreased survival in head and neck squamous cell carcinoma, J Transl Med, 9, 126, 10.1186/1479-5876-9-126 Beji, 2012, Toward the prognostic significance and therapeutic potential of HER3 receptor tyrosine kinase in human colon cancer, Clin Cancer Res, 18, 956, 10.1158/1078-0432.CCR-11-1186 Ho-Pun-Cheung, 2011, EGFR and HER3 mRNA expression levels predict distant metastases in locally advanced rectal cancer, Int J Cancer, 128, 2938, 10.1002/ijc.25639 Narayan, 2009, Trastuzumab-induced HER reprogramming in “resistant” breast carcinoma cells, Cancer Res, 69, 2191, 10.1158/0008-5472.CAN-08-1056 Wheeler, 2008, Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members, Oncogene, 27, 3944, 10.1038/onc.2008.19 Yonesaka, 2011, Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab, Sci Transl Med, 3, 99ra86, 10.1126/scitranslmed.3002442 Arnoletti, 2004, Mechanisms of resistance to Erbitux (anti-epidermal growth factor receptor) combination therapy in pancreatic adenocarcinoma cells, J Gastrointest Surg, 8, 960, 10.1016/j.gassur.2004.09.021 Engelman, 2007, MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling, Science, 316, 1039, 10.1126/science.1141478 Garrett, 2011, Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase, Proc Natl Acad Sci USA, 108, 5021, 10.1073/pnas.1016140108 Chakrabarty, 2011, Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors, Proc Natl Acad Sci USA, 109, 2718, 10.1073/pnas.1018001108 Desbois-Mouthon, 2009, Clin Cancer Res, 15, 5445, 10.1158/1078-0432.CCR-08-2980 Kruser, 2010, Mechanisms of resistance to HER family targeting antibodies, Exp Cell Res, 316, 1083, 10.1016/j.yexcr.2010.01.009 van der Horst, 2005, Anti-HER-3 MAbs inhibit HER-3-mediated signaling in breast cancer cell lines resistant to anti-HER-2 antibodies, Int J Cancer, 115, 519, 10.1002/ijc.20867 Schoeberl, 2010, An ErbB3 antibody, MM-121, is active in cancers with ligand-dependent activation, Cancer Res, 70, 2485, 10.1158/0008-5472.CAN-09-3145 Sala, 2012, An ErbB-3 antibody, MP-RM-1, inhibits tumor growth by blocking ligand-dependent and independent activation of ErbB-3/Akt signaling, Oncogene, 31, 1275, 10.1038/onc.2011.322 Schaefer, 2011, A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies, Cancer Cell, 20, 472, 10.1016/j.ccr.2011.09.003 Aurisicchio, 2012, Novel anti-ErbB3 monoclonal antibodies show therapeutic efficacy in xenografted and spontaneous mouse tumors, J Cell Physiol, 227, 3381, 10.1002/jcp.24037 Blackburn, 2012, A monoclonal antibody to the human HER3 receptor inhibits Neuregulin 1-beta binding and co-operates with Herceptin in inhibiting the growth of breast cancer derived cell lines, Breast Cancer Res Treat, 134, 53, 10.1007/s10549-011-1908-1 Sheng, 2010, An activated ErbB3/NRG1 autocrine loop supports in vivo proliferation in ovarian cancer cells, Cancer Cell, 17, 298, 10.1016/j.ccr.2009.12.047 Schmiedel, 2008, Matuzumab binding to EGFR prevents the conformational rearrangement required for dimerization, Cancer Cell, 13, 365, 10.1016/j.ccr.2008.02.019 Gaborit, 2011, Time-resolved fluorescence resonance energy transfer (TR-FRET) to analyze the disruption of EGFR/HER2 dimers: a new method to evaluate the efficiency of targeted therapy using monoclonal antibodies, J Biol Chem, 286, 11337, 10.1074/jbc.M111.223503 Mondon, 2007, Method for generation of human hyperdiversified antibody fragment library, Biotechnol J, 2, 76, 10.1002/biot.200600205 Talavera, 2009, Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation, Cancer Res, 69, 5851, 10.1158/0008-5472.CAN-08-4518 Li, 2005, Structural basis for inhibition of the epidermal growth factor receptor by cetuximab, Cancer Cell, 7, 301, 10.1016/j.ccr.2005.03.003 Larbouret, 2007, In vivo therapeutic synergism of anti-epidermal growth factor receptor and anti-HER2 monoclonal antibodies against pancreatic carcinomas, Clin Cancer Res, 13, 3356, 10.1158/1078-0432.CCR-06-2302 Zhou, 2006, Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer, Cancer Cell, 10, 39, 10.1016/j.ccr.2006.05.024 Farhan, 2006, Inhibition of xenograft tumor growth and down-regulation of ErbB receptors by an antibody directed against Lewis Y antigen, J Pharmacol Exp Ther, 319, 1459, 10.1124/jpet.106.107318 Nakamura, 2005, Cooperative cell-growth inhibition by combination treatment with ZD1839 (Iressa) and trastuzumab (Herceptin) in non-small-cell lung cancer, Cancer Lett, 230, 33, 10.1016/j.canlet.2004.12.020 McDonagh, 2012, Antitumor activity of a novel bispecific antibody that targets the ErbB2/ErbB3 oncogenic unit and inhibits heregulin-induced activation of ErbB3, Mol Cancer Ther, 11, 582, 10.1158/1535-7163.MCT-11-0820 Huang, 2012, Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiation, Cancer Res, 73, 824, 10.1158/0008-5472.CAN-12-1611 Zhang, 2012, Functional isolation of activated and unilaterally phosphorylated heterodimers of ERBB2 and ERBB3 as scaffolds in ligand-dependent signaling, Proc Natl Acad Sci USA, 109, 13237, 10.1073/pnas.1200105109 Cho, 2002, Structure of the extracellular region of HER3 reveals an interdomain tether, Science, 297, 1330, 10.1126/science.1074611 Aird, 2008, Trastuzumab signaling in ErbB2-overexpressing inflammatory breast cancer correlates with X-linked inhibitor of apoptosis protein expression, Mol Cancer Ther, 7, 38, 10.1158/1535-7163.MCT-07-0370 Yang, 2008, ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation, Nat Cell Biol, 10, 138, 10.1038/ncb1676 Wu, 2010, FOXO1A is a target for HER2-overexpressing breast tumors, Cancer Res, 70, 5475, 10.1158/0008-5472.CAN-10-0176 Chandarlapaty, 2011, AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity, Cancer Cell, 19, 58, 10.1016/j.ccr.2010.10.031 Fu, 2009, MDM2 acts downstream of p53 as an E3 ligase to promote FOXO ubiquitination and degradation, J Biol Chem, 284, 13987, 10.1074/jbc.M901758200 Eckelman, 2006, Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family, EMBO Rep, 7, 988, 10.1038/sj.embor.7400795 Huang, 2011, p53 modulates acquired resistance to EGFR inhibitors and radiation, Cancer Res, 71, 7071, 10.1158/0008-5472.CAN-11-0128 Cao, 2007, Neuregulin-induced ErbB3 downregulation is mediated by a protein stability cascade involving the E3 ubiquitin ligase Nrdp1, Mol Cell Biol, 27, 2180, 10.1128/MCB.01245-06 Qiu, 2002, Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3, Proc Natl Acad Sci USA, 99, 14843, 10.1073/pnas.232580999