The epidermal growth factor receptor (EGFR) is an important component in cancer treatment. EGFR, also called Erb or human epidermal growth factor receptor (HER), is a protein located in the membranes of some cells. The ligands, or molecules, bind to the receptors and start a cascade that controls cell growth. Some types of cancer cells have an abnormally high number of receptors, which leads to uncontrolled growth of tumors.
The ligands activate the epidermal growth factor receptor family. The receptors pair with the ligands, resulting in phosphorylation or the addition of a phosphate group to the molecule. The phosphorylation creates binding sites for the molecules that transmit the signals downstream. The pathway ends with the stimulation of cell proliferation.
The receptors are arranged so that they cross the cell membrane, providing a channel from the outside to the inside of the cell. When the ligands prepare the receptors outside the cell, the receptors translate that signal inside. The signals trigger a cascade that stimulates cell growth and division. In a normal cell, this pathway is tightly regulated to control growth.
However, cancer cells lack the regulatory mechanisms of normal cells. The epidermal growth factor receptor could be overexpressed, which means the cell membrane has too many binding sites. Cells may contain too many copies of the protein, called gene amplification. Some cancer cells also have the ability to make their own ligands, creating cells that are stimulated to multiply.
Overexpression of the epidermal growth factor receptor leads to the classic features of cancer cells: the cells grow too quickly, divide too frequently, produce their own blood supply, and lack the normal signals that initiate natural cell death or apoptosis. Tumors that overexpress EGFR tend to be more advanced and more resistant to chemotherapy and radiation compared to tumors that do not overexpress the protein. Such tumors are also associated with reduced overall survival. The receptor has been identified in breast, colorectal, prostate, ovarian, bladder, and pancreatic cancers, as well as in esophageal, gastric, head and neck, and non-small cell lung cancers.
Targeted therapies seek to interrupt the signaling cascade, preventing EGFR from stimulating cell growth and proliferation. Classes of targeted therapies include monoclonal antibodies, tyrosine kinase inhibitors, and immunotoxin conjugates. These therapies are associated with fewer side effects than traditional chemotherapy agents because they are more specific. The treatment damages fewer healthy cells than when using traditional chemotherapy or radiation.
The signaling cascade can be interrupted at various points. On the cell surface, agents may preferentially bind to receptor sites, preventing ligands from attaching. Targeted therapies can also suppress the receptors and render them inactive. Within the cell, therapies can interrupt the cascade at any point by blocking crucial proteins, thus preventing the signal from reaching its target.