Her1

HER1 is the acronym for "human epidermal growth factor receptor 1" and refers to a receptor tyrosine protein kinase that belongs to the (closely related) family of human epidermal growth factor receptors (EGF receptors). Like HER2, the activated HER1 (Epidermal Growth Factor Receptor, EGFR) stimulates cell proliferation via the RAS-MAP kinase pathway and simultaneously inhibits apoptosis via the mTOR signalling pathway.

The EGF receptor family comprises four closely related members:

1. EGF-R (ErbB-1)
2. HER2/neu (ErbB-2)
3. HER3 (ErbB-3)
4. HER4(ErbB-4).

HER1 receptors, like the other family members of this group of receptors, are transmembrane receptor proteins that receive growth signals and transmit them to various signal transduction chains via their cytoplasmic domain, which acts as a tyrosine-specific protein kinase. Ligands of this receptor group are members of the epidermal growth factor family (EGF).

Overexpression of EGF receptors, including those for HER1 or HER2, indicates a transformation of a healthy cell into a tumor cell (Hossam M et al. 2016). Thus, the number of EGF receptors is significantly increased in numerous malignant tumors (up to 2 million receptors per cell). This overexpression is associated with a worse prognosis, lower survival rates and increased metastasis. This refers mainly to bronchial, breast, prostate, colon and ovarian cancer. In metastatic colorectal carcinomas, EGFR overexpression is over 80%. EGFR-expressing carcinomas are more resistant to chemotherapy.

In detail, two transmembrane EGF receptors dimerise after one of the receptors has bound a growth factor from the EGF family. The isolated binding to one receptor does not yet trigger growth impulses. Only dimerisation with a second receptor leads to activating self-phosphorylation at the cytoplasmic receptor domain and thus to activation of the RAS-MAP kinase pathway. The dimerisation can occur between two identical (homologous) or also between two different (heterologous) ErbB receptors. Homo- or heterodimers are thus formed. Cell proliferation is induced and apoptosis is inhibited via the signal transduction chain in which different phosphorylation reactions play a role.

All four members of the human epidermal growth factor (EGF) receptor (HER) family are involved in human cancers.

The monoclonal antibody cetuximab binds to the receptor HER1, thus preventing the binding of epidermal growth factor. Cetuximab is used in the treatment of colon cancer.

Gefitinib as a small molecule blocks the EGF receptor HER1. Geftinib is used in the treatment of lung cancer. Erlotinib inhibits downstream metabolic pathways of HER1 and HER2 and is used in the treatment of lung cancer and pancreatic cancer.

The effects of e.g. cetuximab and trastuzumab are often associated with co-expression of other HER family members. This can be overcome by a HER ligand binding molecule that binds several EGF-like ligands, thus preventing ligand-dependent receptor activation.

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