Eccles, S. A. (2011) The epidermal growth factor receptor/Erb-B/HER family in normal and malignant breast biology. INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 55 (7-9). pp. 685-696. ISSN 0214-6282

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Abstract

The EGFR/Erb-B receptor tyrosine kinases each play distinct and complementary roles in normal breast development. The four receptors form both homodimers and heterodimers in response to binding by ligands which show selectivity for one or more of the receptors (except Erb-B2). Together with the additional flexibility generated by the formation of different dimer pairs, these signalling networks play key roles in directing a variety of both autocrine and paracrine cellular responses. Complex two-way interactions between mammary epithelial cells and the surrounding stroma direct proliferation, duct formation, branching and terminal differentiation during puberty, pregnancy and lactation, with each receptor and ligand fulfilling distinct roles. Caricatures of the normal role of EGFR/Erb-B signalling resulting in aberrant cellular responses are seen in breast cancers, where over-expression and/or (less commonly) mutation of one or more of the receptors results in enhanced cell proliferation, motility, release of proteases and angiogenic factors. Given their importance in tumour progression and their links with resistance to chemotherapy and anti-endocrine therapy, Erb-B receptors (most notably Erb-B2) have been exploited as therapeutic targets. Monoclonal antibodies (e.g. trastuzumab, pertuzumab) and small molecule tyrosine kinase inhibitors (e.g. lapatinib, afatinib) have shown significant clinical responses in some breast cancer subtypes. Additional approaches include targeted toxins or drugs, peptide vaccines, immunRNase and chaperone inhibitors to deplete Erb-B2 protein levels. Greater understanding of the full spectrum of Erb-B-mediated signalling pathways and their misregulation in breast cancer will provide additional strategies to control malignant progression.

Item Type:	Article
All Authors:	Eccles, S. A.
Additional Information:	ISI Document Delivery No.: 883ST Times Cited: 0 Cited Reference Count: 56 Eccles, Suzanne A. The Institute of Cancer Research; Cancer Research UK[C309/A8274]; NHS SAE is funded by The Institute of Cancer Research and Cancer Research UK programme grant number C309/A8274 awarded to The Cancer Therapeutics Unit (Director, Professor Paul Workman). The ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. I wish to acknowledge the many colleagues, past and present, with whom I have collaborated over the years on aspects of Erb-B biology and translational research, including the late Dr Christopher Dean, erstwhile Head of the Section of Immunology at ICR who pioneered our research on monoclonal antibodies to Erb-B2 and EGFR. I regret that due to space constraints it has not been possible to include all of the relevant references of scientists and clinicians all over the world who have contributed to our current understanding of this important receptor family and their exploitation for patient benefit. U b c press Bilbao Si
Uncontrolled Keywords:	EGFR c-Erb-B2 c-Erb-B3 c-Erb-B4 cancer cancer metastasis intracellular domain erbb2 overexpression mammary development epithelial-cells tumor subtypes expression trastuzumab inhibition basal
Research teams:	ICR divisions > Cancer Therapeutics > Tumour Biology & Metastasis
Depositing User:	Users 11 not found.
Date Deposited:	28 Mar 2012 13:45
Last Modified:	28 Mar 2012 13:45
URI:	http://publications.icr.ac.uk/id/eprint/11465

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