DefinitionThis section has been translated automatically.
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.
ClassificationThis section has been translated automatically.
The EGF receptor family comprises four closely related members:
- EGF-R (ErbB-1)
- HER2/neu (ErbB-2)
- HER3 (ErbB-3)
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General informationThis section has been translated automatically.
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.
PathophysiologyThis section has been translated automatically.
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.
TherapyThis section has been translated automatically.
All four members of the human epidermal growth factor (EGF) receptor (HER) family are involved in human cancers.
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.
LiteratureThis section has been translated automatically.
- Burstein HJ(2005) The New England Journal of Medicine 353: 1652-1564.
- Coussens L et al (1085) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 230: 1132-1139.
- Cunningham D et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337.
- Mates M et al (2015) Systemic targeted therapy for her2-positive early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline". Current Oncology 22 (Suppl 1): 114-122.
- Roy Vet al (2009) Beyond trastuzumab: small molecule tyrosine kinase inhibitors in HER-2-positive breast cancer. The Oncologist 14: 1061-1069
- Rusnak Dwet al. (2001) The characterization of novel, dual ErbB-2/EGFR, tyrosine kinase inhibitors: potential therapy for cancer. Cancer Research 61: 7196-7203