Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer

• Published in: Breast cancer research : BCR Vol. 21; no. 1; p. 43
• Main Authors: Kennedy, Sean P, Han, Jeremy Z R, Portman, Neil, Nobis, Max, Hastings, Jordan F, Murphy, Kendelle J, Latham, Sharissa L, Cadell, Antonia L, Miladinovic, Dushan, Marriott, Gabriella R, O'Donnell, Yolande E I, Shearer, Robert F, Williams, James T, Munoz, Amaya Garcia, Cox, Thomas R, Watkins, D Neil, Saunders, Darren N, Timpson, Paul, Lim, Elgene, Kolch, Walter, Croucher, David R
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 21.03.2019; BioMed Central; BMC
• Subjects: 1-Phosphatidylinositol 3-kinase; Allosteric properties; Animals; Antibodies; Antibodies, Monoclonal, Humanized - pharmacology; Biomarkers; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer cells; Cancer patients; Cancer therapies; Cell activation; Cell culture; Cell Line, Tumor; Cell proliferation; Chemotherapy; Clinical trials; Dimerization; Disease Models, Animal; Displays (Marketing); Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Drug therapy; Enzyme inhibitors; Epidermal growth factor; Epidermal growth factor receptors; ErbB-2 protein; ErbB-3 protein; ERBB2; Extracellular signal-regulated kinase; Family relations; Female; Fluorescent Antibody Technique; Heterodimers; Humans; Immunoglobulins; Immunohistochemistry; Immunotherapy; Kinases; Lapatinib; Ligands; Medical prognosis; Metastasis; Mice; Monoclonal antibodies; Patients; Pertuzumab; Phenols (Class of compounds); Phosphorylation; Promiscuity; Protein interaction; Protein Kinase Inhibitors - pharmacology; Protein Multimerization; Protein-protein interactions; Protein-tyrosine kinase receptors; Receptor tyrosine kinases; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - chemistry; Receptor, ErbB-2 - metabolism; Signal transduction; Signal Transduction - drug effects; Targeted cancer therapy; Trastuzumab; Trastuzumab - pharmacology; Tumor cell lines; Tyrosine; Xenograft Model Antitumor Assays; Xenografts; United States > US; Heterodimers; Breast cancer; Pertuzumab; Receptor tyrosine kinases; ERBB2

The oncogenic receptor tyrosine kinase (RTK) ERBB2 is known to dimerize with other EGFR family members, particularly ERBB3, through which it potently activates PI3K signalling. Antibody-mediated inhibition of this ERBB2/ERBB3/PI3K axis has been a cornerstone of treatment for ERBB2-amplified breast c...