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Targeting the EGF/HER ligand-receptor system in cancer

AutorEsparís-Ogando, Azucena ; Montero, Juan Carlos ; Arribas, Joaquín; Ocaña, Alberto; Pandiella, Atanasio
Palabras claveHER ligands
Anti-HER therapies
Therapy-resistance
HER receptors
Cancer
Fecha de publicación2016
EditorBentham Science Publishers
CitaciónCurrent Pharmaceutical Design 22(39): 5887-5898 (2016)
ResumenReceptor tyrosine kinases (RTKs) are a superfamily of transmembrane proteins that mediate intracellular signaling by phosphorylating substrate proteins involved in cell proliferation, survival, differentiation or migration. The Human Epidermal growth factor Receptor (HER) family belongs to the RTKs superfamily, and comprises four members: EGFR (epidermal growth factor receptor), HER2, HER3 and HER4. Physiologically, these receptors are activated by the ligands of the EGF family. In solid tumors other mechanisms of activation, such as overexpression or molecular alterations have been reported, and have been linked to tumour initiation/progression. Because of that, several strategies have been developed to target HER receptors and include i) antibody-based therapies using monoclonal antibodies against the extracellular domain of these receptors, and ii) small molecule tyrosine kinase inhibitors (TKIs) against the intracellular kinase domain. In this review we will provide basic information about biological aspects of HER receptors and their ligands as well as the therapeutic strategies to target them. We also summarize general mechanisms of resistance generated in patients to such anti-HER therapies.
URIhttp://hdl.handle.net/10261/168742
Identificadoresdoi: 10.2174/1381612822666160715132233
e-issn: 1873-4286
issn: 1381-6128
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