The epidermal growth factor receptor, or EGFR, is a type of protein found on the surface of many cells throughout the body. This protein acts as a receiver, interpreting signals from outside the cell and relaying them inward. EGFR plays a fundamental role in cell communication, enabling cells to respond to their environment and coordinate various biological processes.
How EGFR Functions in Healthy Cells
In healthy cells, EGFR functions like a “lock and key” system, awaiting specific external signals. When growth factors bind to the EGFR, it initiates a series of events. This binding causes two EGFR proteins to come together, a process called dimerization, which activates the receptor.
Once activated, the EGFR triggers a cascade of signals inside the cell by adding phosphate groups to specific internal regions, known as autophosphorylation. This internal signaling then activates various pathways within the cell, including the Ras/MAPK and PI3K/Akt pathways. These pathways ultimately lead to outcomes such as promoting cell growth, encouraging cell division, supporting cell survival, and guiding cell differentiation, all necessary for maintaining healthy tissues and normal physiological processes.
When EGFR Contributes to Disease
While EGFR signaling is well-regulated in healthy cells, it can become dysregulated, leading to uncontrolled cell growth, particularly in various cancers. One way this dysfunction occurs is through overexpression, where cells produce an abnormally high number of EGFR proteins on their surface. An increased number of receptors makes the cell hypersensitive to growth signals, even low levels, leading to excessive activation of growth pathways.
Another significant mechanism involves mutations within the EGFR gene itself. These genetic changes can cause the EGFR protein to become constantly active, even without a growth factor binding to it. For example, common mutations in lung cancer involve deletions in exon 19 or changes in exon 21. This continuous activation promotes uncontrolled cell division and survival, fostering tumor growth and contributing to metastasis. Such dysregulation is observed in several cancer types, including non-small cell lung cancer, colorectal cancer, and head and neck cancers.
Targeting EGFR for Treatment
Understanding the role of EGFR in cancer has led to the development of targeted therapies designed to block abnormal signaling. These treatments, known as EGFR inhibitors, work by interfering with the protein’s activity. Two main types of inhibitors exist: small molecule inhibitors and monoclonal antibodies. Small molecule inhibitors, such as gefitinib or erlotinib, enter the cell and block the internal signaling portion of the EGFR protein.
Monoclonal antibodies, like cetuximab, are protein-based drugs that bind to the external part of the EGFR, preventing growth factors from attaching and activating the receptor. These therapies are often part of precision oncology, where patients undergo genetic testing to identify specific EGFR mutations. If a patient’s tumor has certain EGFR mutations, they are more likely to respond to these targeted drugs, leading to more effective treatment outcomes. Despite their effectiveness, some tumors can develop resistance to these therapies over time through additional mutations or alternative signaling pathways.