Epidermal growth factor receptor and its medical applications

Image

The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands.

The epidermal growth factor receptor is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1), HER2/neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). In many cancer types, mutations affecting EGFR expression or activity could result in cancer.

Medical applications

Drug target

The identification of EGFR as an oncogene has led to the development of anticancer therapeutics directed against EGFR (called "EGFR inhibitors", EGFRi), including gefitinib,  erlotinib, afatinib, brigatinib and icotinib for lung cancer, and cetuximab for colon cancer. More recently AstraZeneca has developed Osimertinib, a third generation tyrosine kinase inhibitor.

Many therapeutic approaches are aimed at the EGFR. Cetuximab and panitumumab are examples of monoclonal antibody inhibitors. However the former is of the IgG1 type, the latter of the IgG2 type; consequences on antibody-dependent cellular cytotoxicity can be quite different. Other monoclonals in clinical development are zalutumumab, nimotuzumab, and matuzumab. The monoclonal antibodies block the extracellular ligand binding domain. With the binding site blocked, signal molecules can no longer attach there and activate the tyrosine kinase.

Another method is using small molecules to inhibit the EGFR tyrosine kinase, which is on the cytoplasmic side of the receptor. Without kinase activity, EGFR is unable to activate itself, which is a prerequisite for binding of downstream adaptor proteins. Ostensibly by halting the signaling cascade in cells that rely on this pathway for growth, tumor proliferation and migration is diminished. Gefitinib, erlotinib, brigatinib and lapatinib (mixed EGFR and ERBB2 inhibitor) are examples of small molecule kinase inhibitors.

There are several quantitative methods available that use protein phosphorylation detection to identify EGFR family inhibitors.

New drugs such as osimertinib, gefitinib, erlotinib and brigatinib directly target the EGFR. Patients have been divided into EGFR-positive and EGFR-negative, based upon whether a tissue test shows a mutation. EGFR-positive patients have shown a 60% response rate, which exceeds the response rate for conventional chemotherapy.

The most common adverse effect of EGFR inhibitors, found in more than 90% of patients, is a papulopustular rash that spreads across the face and torso; the rash's presence is correlated with the drug's antitumor effect. In 10% to 15% of patients the effects can be serious and require treatment.

Some tests are aiming at predicting benefit from EGFR treatment, as Veristrat.

Laboratory research using genetically engineered stem cells to target EGFR in mice was reported in 2014 to show promise. EGFR is a well-established target for monoclonal antibodies and specific tyrosine kinase inhibitors.

Target for imaging agents

Imaging agents have been developed which identify EGFR-dependent cancers using labeled EGF. The feasibility of in vivo imaging of EGFR expression has been demonstrated in several studies.

Journal of Cancer Research and Immuno-Oncology is an open access rapid peer reviewed journal in the field of cancer research. Journal announces papers for the upcoming issue. Interested can submit their manuscript through online portal.

Submit manuscript at https://www.longdom.org/submissions/cancer-research-immuno-oncology.html or send as an e-mail attachment to the Editorial Office at immunooncology@emedscholar.com

Media contact:

Maegan Smith

Managing Editor

Journal of Cancer Research and Immuno-Oncology

Mail ID: immunooncology@emedscholar.com

WhatsApp:  180-23424982