The epidermal growth factor receptor family: Biology driving targeted therapeutics

Abstract

The epidermal growth factor family of receptor tyrosine kinases (ErbBs) plays essential roles in regulating cell proliferation, survival, differentiation and migration. The ErbB receptors carry out both redundant and restricted functions in mammalian development and in the maintenance of tissues in the adult mammal. Loss of regulation of the ErbB receptors underlies many human diseases, most notably cancer. Our understanding of the function and complex regulation of these receptors has fueled the development of targeted therapeutic agents for human malignancies in the last 15 years. Here we review the biology of ErbB receptors, including their structure, signaling, regulation, and roles in development and disease, then briefly touch on their increasing roles as targets for cancer therapy.

Genomics implicates adaptive and innate immunity in Alzheimer's and Parkinson's diseases

“…Specific examples included: in MS (e.g., T‐helper cell differentiation, role of macrophages, fibroblasts, and endothelial cells in RA, B cell receptor signaling, dendritic cell maturation, PI3K signaling in B lymphocytes, CD40 signaling; PKC θ signaling in T lymphocytes, NF‐ κ B activation by viruses); in PD (e.g., dendritic cell maturation – shared with MS, graft‐versus‐host disease signaling, altered T cell and B cell signaling in rheumatoid arthritis); in AD (IL‐8 signaling, IL‐12 signaling and production in macrophages, Fc epsilon RI signaling, Fc γ receptor‐mediated phagocytosis in macrophages and monocytes, role of pattern recognition receptors in recognition of bacteria and viruses, natural killer cell signaling); and in ALS (e.g., NF‐ κ B signaling). The value of the IPA method was also demonstrated in providing significant signals for other pathways previously implicated in the pathogenesis of AD, including CREB signaling in neurons,41 neuregulin signaling, and ErbB signaling 42. For the IPA diseases/biological functions analysis, various cancers came up as most strongly significant for all the disorders.…”

Conformational flexibility of the ErbB2 ectodomain and trastuzumab antibody complex as revealed by molecular dynamics and principal component analysis

“…These receptors are engaged in the regulation of many processes such as cell proliferation, differentiation and apoptosis. Loss of regulation of these receptors has a great impact in a number of human diseases, such as cancer [1,2]. All EGFR receptors contain three different regions: an extracellular (ectodomain, ECD) ligand-binding region, a single membrane-spanning domain and a cytoplasmatic tyrosine kinase domain.…”

“…These receptors are engaged in the regulation of many processes such as cell proliferation, differentiation and apoptosis. Loss of regulation of these receptors has a great impact in a number of human diseases, such as cancer [1,2].…”

Epidermal growth factor signalling and bone metastasis

“…On binding, ERBBs form homo-or heterodimers and activate multiple important pathways involving effectors such as rat sarcoma viral oncogene homologue (RAS)/mitogen-activated protein kinase, phosphatidylinositol 3-kinase-AKT, mammalian target of rapamycin, signal transducer and activator of transcription, SRC tyrosine kinase, phospholipase C-g1/protein kinase C (PKC) and p27 (Hynes and Lane, 2005;Wieduwilt and Moasser, 2008). The activation of these pathways has essential functions in many aspects of development and tissue homoeostasis.…”