Epidermal Growth Factor Family

The epidermal growth factor (EGF) family of tyrosine kinase receptors consists of four receptors (EGFR, ErbB2, ErbB3 and ErbB4) and more than a dozen ligands. Ligand binding to the extracellular domain of the receptor results in activation of the receptor. The activated receptor can dimerize with other EGF receptors followed by phosphorylation of tyrosine residues on the receptors. The epidermal growth factor receptor (EGFR) is one of the most frequently overexpressed proteins in various cancers including lung cancer, and signaling through this receptor has been known to cause tumor progression as well as resistance to different treatments. Therefore, the EGFR has become an attractive target for various treatment strategies. The two most commonly used tyrosine kinase inhibitors targeting EGFR are gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774).However, overall response rates have been relatively disappointing (10-15%) in studies that examine all NSCLC patients collectively. It is a possibility that not all lung cancer patients are suitable for erlotinib treatment and that patients should be selected for this treatment. Various parameters, such as type of the tumor, smoking history, gender and ethnicity. Despite this, response rates are not as promising as expected. Expression and mutation status of the EGFR has also been used to predict response, and it has been reported that patients expressing high amounts of the EGFR show better response to erlotinib. Furthermore, recent studies also suggest that the combined expression of the EGF receptors but not the individual receptor in a tumour is important when analysing the outcome of the disease or drugs targeting these receptors. However, analysis of expression of the EGFR and the presence of mutations requires a tumor biopsy, which is not possible to get in all situations. Thus, there is a need to develop non-invasive methods that can identify the subset of patients which are most likely to benefit from drugs targeting these receptors.

Epidermal Growth Factor Family

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