**2. Focus on human epidermal growth factor receptors (HERs)**

Membrane-bound human epidermal growth factor receptors (HERs) consist of a ligand-binding domain at the extracellular surface, a single transmembrane segment, and a cytoplasmic portion harboring the protein kinase activity. The HER family includes four structurally related members, namely the epidermal growth factor receptor (EGFR, also known as HER1), HER2, HER3, and HER4. Ligand binding to the extracellular domain triggers conformational changes of receptors that form HER-dimerization, and subsequently, activates downstream a signaling cascade and ultimately stimulates tumor cell proliferation. Therefore, HERs are the most innovative targets for GC treatment.
