The Epidermal Growth Factor Receptor (EGFR) is a protein found on the surface of human cells. It plays an important role in cell communication and growth, receiving signals that instruct cells. When external signals bind to EGFR, they initiate a cascade of events inside the cell.
The Role of EGFR in Our Bodies
EGFR normally functions as a cellular antenna, receiving signals that tell cells to grow, divide, and repair themselves. This protein belongs to a family of receptor tyrosine kinases (RTKs) that are embedded in the cell membrane. When growth factors like epidermal growth factor (EGF) bind to EGFR, it triggers a shape change. This activates the internal tyrosine kinase domain, which then adds phosphate groups to other proteins inside the cell.
This phosphorylation acts like a switch, turning on various pathways that promote cell growth, DNA synthesis, and cell proliferation. The process is tightly regulated in healthy cells, ensuring that cell division and tissue maintenance occur in a controlled manner. This normal signaling is important for processes like wound healing and tissue repair.
When EGFR Goes Wrong: Mutations in Cancer
When the EGFR gene undergoes specific changes, known as mutations, the protein’s behavior can be significantly altered. These mutations can cause the EGFR protein to become constantly active, sending continuous “grow” signals to the cell, even without external growth factors present. This uncontrolled signaling leads to unregulated cell division and survival, which are hallmarks of cancer.
These specific genetic changes are often referred to as “driver mutations” because they are a primary cause of cancer development and progression in certain malignancies, particularly non-small cell lung cancer (NSCLC). There are many different types of EGFR mutations, often identified by their location within the gene, such as deletions in exon 19 or point mutations like L858R in exon 21. Each unique alteration, such as the hypothetical “108 mutation,” represents a precise change in the EGFR gene that can lead to its abnormal activation.
Finding EGFR Mutations and Guiding Treatment
Identifying specific EGFR mutations in patients is important for guiding cancer treatment decisions and enabling precision medicine. These mutations are primarily detected through genetic testing of tumor tissue, typically obtained via a biopsy. If a tissue biopsy is difficult or not feasible, a “liquid biopsy” can be performed, which involves analyzing circulating tumor DNA (ctDNA) from a blood sample. This minimally invasive method has shown high sensitivity for detecting EGFR mutations.
Once an EGFR mutation is identified, it indicates that the patient’s cancer may respond to targeted therapies. A class of drugs called tyrosine kinase inhibitors (TKIs) are specifically designed to block the activity of the mutated EGFR protein. These medications, such as gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib, work by interfering with the overactive signaling pathways driven by the mutated EGFR, thereby halting cancer cell growth and proliferation. This targeted approach often leads to more effective treatments with fewer side effects compared to traditional chemotherapy, offering benefits for patients with EGFR-mutated cancers.