Home » Health & Wellness » Cancer Treatment » Cancer Drugs that Inhibit Epidermal Growth Factor Receptors

Cancer Drugs that Inhibit Epidermal Growth Factor Receptors

© David Olle

Cancer drugs that inhibit epidermal growth factor receptors

Epidermal growth factor receptors are found in the cell membranes. When activated, these receptors initiate a signaling process that regulates cell growth. Since many cancers have excessive activation of these receptors, drugs have been developed to inhibit their functioning.

What are epidermal growth factor receptors and what are their functions?

Epidermal growth factor receptors are found in the cell membrane, extending from the exterior to the interior of the cell. The external part contains the actual receptor that binds to specific molecules, such as epidermal growth factor and transforming growth factor alpha. This binding causes the receptor to form a complex, known as dimerization, with another receptor. Structural changes then occur in the internal portion of the receptor, leading to activation of its kinase enzyme. This activation takes place through the addition of a phosphate group to tyrosine, an amino acid residue on the receptor protein. The kinase enzyme begins an extensive chemical signaling process that regulates cell growth. The signaling process extends into the nucleus, where genes are activated to form proteins that are essential for cell proliferation, control of apoptosis (cell death), and angiogenesis (blood vessel formation).

Why are epidermal growth factor receptors important in cancer?

One of the characteristics of many cancers is an abnormal increase in the activity of epidermal growth factor receptors. Tumors that show overexpression of epidermal growth factor receptors include cancers of the lung (non-small cell), colon and rectum, breast, pancreas, prostate, ovary, head and neck, esophagus, and brain (glioblastoma). This increased activity leads to uncontrolled cell growth, with decreased apoptosis and increased angiogenesis. The overexpression of receptors leads to activation of other genes that promote cancer growth through such means as invasion and metastasis, and resistance to chemotherapy and radiotherapy.

The development of drugs that inhibit epidermal growth factor receptors

There are two basic approaches to the development of drugs that inhibit epidermal growth factor receptors 3:

1. Monoclonal antibodies that bind to the external receptor.

The antibodies compete with growth factors for binding, and block dimerization and activation of the tyrosine kinase enzyme. For a discussion of monoclonal antibodies, please read my January 16, 2001 article on the topic.

Cetuximab (trade name Erbitux) is approved by the FDA for use in advanced colorectal cancer. Clinical trials have indicated that cetuximab can enhance the antitumor effects of the chemotherapeutic drug cisplatin in head and neck cancer. This product is a so-called chimeric antibody prepared from laboratory mice, so has the disadvantage of eventually stimulating an antibody response from the patient's body. When chimeric antibodies are used on a long-term basis, they will be destroyed by the body's immune system before they can exert their anti-cancer effect.