Mutations are alterations or changes in the sequence of DNA (genetic material). They can be perceived as a change in the sequence of the DNA code. Normal codes are needed for the smooth functioning of the cells and tissues in the body. The occurrence of mutations can cause several health conditions. Moreover, mutations may affect the action of medication against a particular disease. Some mutations may be favorable as well. Such mutations provide mechanisms to adapt better to the changing environment (evolution). Mutations can cause uncontrolled multiplication of the cells leading to cancer. With the advancements in medical science and technology, newer treatment options are emerging that target and destroy the cancer cells with minimal or no harm to normal or healthy cells. Mutations in cancer cells may give them advantages aiding the progression and spread (metastasis) of cancer. Conversely, mutations may provide benefits as far as treatment is concerned because they may create certain microscopic structural changes in the cancer cells. These structural changes help in the targeted delivery of drugs to the cancer cells. This means the drug can go and attach to the cancer cell and kill it.
What is an EGFR mutation?
Mutations can cause changes in proteins present on the surface of cells if they affect gene coding for a surface protein. One such protein is called epidermal growth factor receptor (EGFR). This protein is most commonly found on the skin cells, although it can be found anywhere in the body. The function of the EGFR protein is to help the cells grow and divide (increase in number). The EGFR protein is produced by information provided by the <i>EGFR</i> gene.
Normally, this gene is regulated, which means there is a switch present in the cell to turn it on when cell growth and division are needed and switch it off when not needed. In certain types of cancer, such as EGFR-positive non-small cell lung cancer (NSCLC), a mutation in the <i>EGFR</i> gene causes the EGFR protein to persistently remain in the “on” position. NSLC is the most common variety of lung cancer accounting for 80 to 85 percent of the cases. The other variety is called small cell lung cancer accounting for the rest of the cases of lung cancer.
The <i>EGFR</i> mutation causes uncontrolled cell growth (cancer). The abnormal <i>EGFR</i> gene is, thus, a type of tumor marker or biomarker that can be detected through lab tests. Tumor cells carrying the abnormal <i>EGFR</i> gene are called EGFR-positive cancer cells. This protein was the first tumor marker identified for the targeted treatment of EGFR-positive lung cancer.
EGFR-positive lung cancer is more commonly seen in
- People who have never smoked or only smoked a little
- People with a type of NSCLC cancer called lung adenocarcinoma
- Young adults with lung cancer. About 50 percent of lung cancer seen in young adults is positive for EGFR mutations.
- In people of Asian or East Asian heritage
<i>EGFR</i> mutations can be tested by performing a gene analysis in a lab on a sample of cancerous tissue collected from the lung (biopsy). A biopsy is the most accurate way to look for <i>EGFR</i> mutations. Doctors may detect <i>EGFR</i> mutations by collecting blood samples that may contain the tumor cells shed from the lungs. This is called liquid biopsy.
What is an EGFR exon 20 mutation?
Various types of mutations can occur in the epidermal growth factor receptor <i>(EGFR)</i> gene depending upon the site involved in the gene. The <i>EGFR</i> gene has several sections (expressed as numbers) called exons. Mutations can occur on any of these exons. The most common <i>EGFR</i> mutations include missing genetic material (deletion) on exon 19 (19-del) or damage to exon 21 (21-L858R). These two mutations are responsible for about 85 percent of <i>EGFR</i> mutations seen in lung cancer. <i>EGFR</i> exon 20 mutations involve a specific site on the <i>EGFR</i> gene called the exon 20 (region on the <i>EGFR</i> gene that contains part of the genetic code required for the formation of EGFR protein).
Why is knowing the type of an EGFR mutation important?
Knowing the type of mutation occurring in the epidermal growth factor receptor <i>(EGFR)</i> gene is important for determining the treatment of non-small cell lung cancer (NSLC). For example, <i>EGFR </i>19 deletion and <i>EGFR</i> L858R point mutations respond to targeted therapies called tyrosine kinase inhibitors (TKIs). The choice of the drug may vary depending on the specific mutation. These drugs include
- Tarceva (erlotinib)
- Iressa (gefitinib)
- Gilotrif (afatinib)
- Tagrisso (osimertinib)
- Vizimpro (dacomitinib)
Cancer with <i>EGFR</i> exon 20 mutations, however, does not respond to TKIs.
There are other drugs that may be used in cancer with an exon 20 mutation with more success. One such example is the drug Rybrevant (amivantamab). It is a monoclonal antibody (a lab-made version of a specific immune system protein). It targets two proteins that help cancer cells grow: EGFR and MET.
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American Lung Association: "EGFR and Lung Cancer." https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/learn-about-lung-cancer/how-is-lung-cancer-diagnosed/lung-cancer-tumor-testing/egfr