The role of the ErbB3 receptor in signal transduction is to augment the signaling repertoire of active heterodimeric ErbB receptor complexes through activating the PI3K/AKT pathway, which in turn promotes survival and proliferation. ErbB3 has recently been proposed to be involved in acquired resistance to tyrosine kinase inhibitors (TKIs), and is therefore a promising new drug cancer target. Since ErbB3 is a kinase defective receptor, it cannot be targeted by small molecule inhibitors, whereas monoclonal antibodies may offer a viable strategy for pharmacological intervention. In this study, we have utilized DNA electroporation (DNA-EP) to generate a set of novel hybridomas directed against human ErbB3, which have been characterized for their biochemical and functional properties and selected for their ability to negatively regulate the ErbB3-mediated signaling pathway. In vitro, the anti-ErbB3 antibodies modulate the growth rate of cancer cells of different origins. In vivo they show antitumoral properties in a xenograft model of human pancreatic tumor and in the ErbB2-driven carcinogenesis genetically engineered mouse model (GEMM) for mammary tumor, the BALB/neuT. Our data confirm that downregulating the ErbB3-mediated signals with the use of anti-ErbB3 monoclonal antibodies is both feasible and relevant for therapeutic purposes and provides new opportunities for novel anti-ErbB3 combinatory strategies for cancer treatment. J. Cell. Physiol. 227: 33813388, 2012. (C) 2011 Wiley Periodicals, Inc.

Novel anti-ErbB3 monoclonal antibodies show therapeutic efficacy in xenografted and spontaneous mouse tumors / Luigi, Aurisicchio; Emanuele, Marra; Laura, Luberto; Carlomosti, Fabrizio; Claudia De, Vitis; Alessia, Noto; Zeynep, Gunes; Giuseppe, Roscilli; Giuseppe, Mesiti; Mancini, Rita; Alimandi, Maurizio; Gennaro, Ciliberto. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 227:10(2012), pp. 3381-3388. [10.1002/jcp.24037]

Novel anti-ErbB3 monoclonal antibodies show therapeutic efficacy in xenografted and spontaneous mouse tumors

Luigi Aurisicchio;CARLOMOSTI, FABRIZIO;MANCINI, RITA;ALIMANDI, MAURIZIO;
2012

Abstract

The role of the ErbB3 receptor in signal transduction is to augment the signaling repertoire of active heterodimeric ErbB receptor complexes through activating the PI3K/AKT pathway, which in turn promotes survival and proliferation. ErbB3 has recently been proposed to be involved in acquired resistance to tyrosine kinase inhibitors (TKIs), and is therefore a promising new drug cancer target. Since ErbB3 is a kinase defective receptor, it cannot be targeted by small molecule inhibitors, whereas monoclonal antibodies may offer a viable strategy for pharmacological intervention. In this study, we have utilized DNA electroporation (DNA-EP) to generate a set of novel hybridomas directed against human ErbB3, which have been characterized for their biochemical and functional properties and selected for their ability to negatively regulate the ErbB3-mediated signaling pathway. In vitro, the anti-ErbB3 antibodies modulate the growth rate of cancer cells of different origins. In vivo they show antitumoral properties in a xenograft model of human pancreatic tumor and in the ErbB2-driven carcinogenesis genetically engineered mouse model (GEMM) for mammary tumor, the BALB/neuT. Our data confirm that downregulating the ErbB3-mediated signals with the use of anti-ErbB3 monoclonal antibodies is both feasible and relevant for therapeutic purposes and provides new opportunities for novel anti-ErbB3 combinatory strategies for cancer treatment. J. Cell. Physiol. 227: 33813388, 2012. (C) 2011 Wiley Periodicals, Inc.
2012
01 Pubblicazione su rivista::01a Articolo in rivista
Novel anti-ErbB3 monoclonal antibodies show therapeutic efficacy in xenografted and spontaneous mouse tumors / Luigi, Aurisicchio; Emanuele, Marra; Laura, Luberto; Carlomosti, Fabrizio; Claudia De, Vitis; Alessia, Noto; Zeynep, Gunes; Giuseppe, Roscilli; Giuseppe, Mesiti; Mancini, Rita; Alimandi, Maurizio; Gennaro, Ciliberto. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 227:10(2012), pp. 3381-3388. [10.1002/jcp.24037]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/431954
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