The Epidermal Growth Factor Receptor (EGFR) is a protein located on the surface of human cells. This protein acts as a receiver, binding to specific signals from outside the cell. Its role is to help cells respond to their environment.
The Function of EGFR
EGFR normally functions as a transmembrane protein, spanning the cell membrane. When growth factors, such as epidermal growth factor (EGF), bind to the outer portion of EGFR, two EGFR proteins join together, a process called dimerization, which activates the receptor.
Once activated, EGFR initiates signaling pathways inside the cell, stimulating its intrinsic protein-tyrosine kinase activity. This activity leads to the phosphorylation of tyrosine residues, which then recruits other proteins. These downstream signals instruct the cell to grow, divide, and survive.
When EGFR Goes Wrong: Mutations
A gene mutation refers to a change in the DNA sequence of a gene. For the EGFR gene, specific mutations can alter the EGFR protein, causing it to become continuously active, even without external signals. This constant activation leads to uncontrolled cell growth and division, a hallmark of cancer.
These activating mutations in the EGFR gene are linked to certain cancers, most notably non-small cell lung cancer (NSCLC). In NSCLC, EGFR mutations are found in approximately 10-15% of cases in the United States, with a higher incidence in Asian populations. Common EGFR mutations include deletions in exon 19 or a specific point mutation in exon 21 (L858R). These alterations cause the receptor protein to constantly signal for proliferation and survival, contributing to tumor formation.
Identifying EGFR Mutations
Detecting EGFR mutations is an important step in personalized cancer treatment, guiding treatment decisions. Doctors primarily use two methods to identify these mutations. One common approach is a tissue biopsy, where a small tumor sample is analyzed to identify genetic changes, including EGFR mutations, through next-generation sequencing (NGS).
Another method is a liquid biopsy, a less invasive blood test. This test detects circulating tumor DNA (ctDNA) released by cancer cells into the bloodstream. While a liquid biopsy can identify EGFR mutations and is useful when a tissue biopsy is not feasible, a tissue biopsy is generally preferred for initial diagnosis due to the possibility of false-negative results with liquid biopsies.
Targeted Treatments for EGFR Mutations
Targeted therapy represents a different approach to cancer treatment compared to traditional chemotherapy. Unlike chemotherapy, which broadly attacks rapidly dividing cells, targeted therapies specifically block the activity of proteins involved in cancer growth. For patients with EGFR mutations, specific drugs called EGFR tyrosine kinase inhibitors (TKIs) are designed to interrupt the signals from the mutated EGFR protein.
These TKIs work by binding to and inhibiting the overactive EGFR, thereby slowing or stopping cancer cell growth. Several generations of EGFR TKIs exist, with newer ones developed to improve effectiveness or overcome drug resistance. Examples of these inhibitors include osimertinib, gefitinib, erlotinib, and afatinib, each with specific indications based on the type of EGFR mutation. Targeted therapies often offer benefits such as improved quality of life and better tumor control for patients with EGFR mutations.