Title:Targeting the EGF/HER Ligand-Receptor System in Cancer
VOLUME: 22 ISSUE: 39
Author(s):Azucena Esparís-Ogando, Juan Carlos Montero, Joaquín Arribas, Alberto Ocaña and Atanasio Pandiella
Affiliation:Instituto de Biología Molecular y Celular del Cáncer-CIC, Campus Miguel de Unamuno, s/n, 37007- Salamanca, Spain.
Keywords:Cancer, HER receptors, HER ligands, anti-HER therapies, therapy-resistance.
Abstract:Receptor 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.
