Egf receptors

EGf refers to a family of transmembrane growth receptors (see below growth factors) to which 4 closely related receptor tyrosine kinases belong: EGFR1/HER1 (ErbB-1), HER2/c-new (ErbB-2), HER3 (ErbB-3) and HER4 (ErbB-4). EGF receptors are encoded by the EGFR gene. EGF receptors belong to the group of receptor tyrosine kinases which, among other things, can activate the MAP kinase pathway (MAPK pathway) as an important oncogenic signalling pathway.

Activation of the EGF receptor is achieved by extracellular binding of ligands from the epidermal growth factor family such as:

• EGF
• Transforming Growth Factor-a (TGF-a)
• Heparin-binding EGF
• Amphiregulin
• Betacellulin
• epiregulin or
• Neuregulin G2b and others (see epidermal growth factors below).

After receptor binding, the RAS-MAP kinase pathway is activated (signal transduction). This stimulates cell growth and prevents apoptosis.

The EGF receptor is ubiquitously expressed in the body's tissue. In the cell membrane of a healthy cell there are about 40,000-100,000 EGFR molecules.

The overexpression of EGF receptors often indicates the transformation of a healthy cell into a tumor cell. Increased EGFR levels are detectable in numerous tumor types (up to 2 million receptors per cell are known). The overexpression of the receptors in tumor cells is associated with a worse prognosis, lower survival rates and increased metastasis. They are particularly common in bronchial, breast, prostate, colon and ovarian cancer. In metastatic colorectal carcinomas, EGFR overexpression is over 80%. EGFR-expressing carcinomas are more resistant to chemotherapy.

Tyrosine kinase inhibitors or EGFR inhibitors prevent the activation of the receptor by competitive binding and block the oncogenic signal of EGFR and thus tumor growth. Already successfully tested and approved substances are:

• gefitinib (Iressa)
• Erlotinib (Tarceva)
• Cetuximab (Erbitux; e.g. in colorecatal carcinoma; see side effects under exanthema, akneiformes).

1. Bayes M et al (2006) Gateways to clinical trials. Methods Find Exp Clin Pharmacol 28: 31-63
2. Knight LA et al (2004) The in vitro effect of gefitinib ('Iressa') alone and in combination with cytotoxic chemotherapy on human solid tumours. BMC Cancer 23: 83
3. Saltz LB et al (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22: 1201-1208