EGFR
Meaning of EGFR: Written in lower case as eGFR the same four letters mean an estimate of kidney function, an entirely unrelated measurement.
Definition of EGFR
EGFR, short for epidermal growth factor receptor, is a protein that sits in the surface membrane of many cells with one end outside and one end inside. When a matching growth factor binds the outer end, the inner end switches on a chain of signals telling the cell to grow and divide. The gene coding for it carries the same name.
How does the receptor work?
EGFR belongs to a family of receptors that span the cell membrane. Growth factor binding on the outside causes two receptor molecules to pair up, and that pairing activates an enzyme region on the inner end. The activated enzyme attaches phosphate groups to other proteins, starting a relay that reaches the nucleus and switches on genes for growth and division. Once the message has been delivered the receptor is normally drawn inside the cell and broken down, so the signal is limited in time. Related receptors in the same family include HER2, formally human epidermal growth factor receptor 2, and members of the family can pair with each other as well as with themselves.
What goes wrong in cancer?
Two distinct faults occur. In some tumors the cell carries far more copies of the receptor than normal, so ordinary amounts of growth factor produce an exaggerated signal. In others the gene itself is mutated so that the inner enzyme is permanently switched on, signaling continuously whether or not any growth factor is present. The second happens in a subset of non-small cell lung cancer, particularly adenocarcinoma, and it leaves the tumor dependent on that single pathway, which is precisely what a targeted drug exploits.
What does testing establish?
| Non-small cell lung cancer | Colorectal cancer | |
|---|---|---|
| What is tested | The EGFR gene, for specific mutations | The RAS and BRAF genes, for mutations |
| Type of drug involved | A small molecule blocking the enzyme inside the cell | An antibody blocking the receptor from outside |
| What the result predicts | An EGFR mutation predicts response to the blocking drug | A RAS mutation predicts a lack of benefit from the antibody |
The two are easily conflated and in fact work in opposite directions. In lung cancer the presence of an EGFR mutation is what selects the treatment. In colorectal cancer, antibodies targeting EGFR are used without requiring an EGFR mutation, and a mutation further down the same pathway, in a RAS gene, predicts that the drug will not help, because the signal is then generated below the point at which the antibody blocks it. Resistance eventually develops in most cases through additional changes along the pathway, which is why tissue or blood is retested when a treatment stops working.
Also known as
Used in a sentence
The tumor sample was tested for EGFR mutations to guide selection of targeted therapy.
Good to know
Tumor testing for EGFR mutations identifies cancers likely to respond to a drug targeting this receptor, and the abbreviation should not be confused with eGFR in lower case, the estimated glomerular filtration rate used to describe kidney function.