EGFR/Her-3 Antibodies

Target Information

EGFR, epidermal growth factor receptor, is a receptor tyrosine kinases that signals in response to various growth factors. Overexpression has been linked to numerous types of cancer and EGFR is the target of both biological and small molecular therapeutics. EGFR is encoded by the EGFR gene located on chromosome 7 in humans. EGFR belongs to the HER/ERbB family of proteins that includes three other receptor tyrosine kinases, ERbB2, ERbB3, ERbB4. EGFR is a transmembrane receptor and binding of its cognate ligands such as EGF (Epidermal Growth Factor) and TGF alpha (Transforming Growth Factor alpha) to the extracellular domain leads to EGFR dimerization followed by autophosphorylation of the tyrosine residues in the cytoplasmic domain. Overexpression is observed in tumors of the head and neck, brain, bladder, stomach, breast, lung, endometrium, cervix, vulva, ovary, esophagus, stomach and in squamous cell carcinoma.

ErbB3 (c-erbB-3/HER-3) is a member of the type I family of growth factor receptors and binds to ligands in the heregulin family. ErbB3 is over-expressed in a variety of tumors in the prostate, bladder, breast, stomach, pancreas, and colon. Heregulin and EGF stimulate tyrosine phosphorylation of c-erbB-3 to different extents. The ErbB3 gene is located on the long arm of human chromosome 12 (12q13) and is transcribed into a 6. 2kb mRNA which is translated into a 160/180 kDa glycoprotein. The ErbB3 gene encodes a transmembrane receptor tyrosine kinase due to alternative splicing and forms heterodimers with other EGF receptor family members that have kinase activity. Heterodimerization leads to the activation of pathways that lead to cell proliferation or differentiation. Alternate transcriptional splice variants encoding different isoforms of ErbB3 have been characterized. One ErbB3 isoform lacks the intermembrane region, is secreted outside the cell, and acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized.