The Epidermal Growth Factor Receptor (EGFR) is a protein on the surface of cells that helps regulate normal cell growth and division. In medicine, a biomarker is a measurable characteristic in the body that indicates a particular biological state. When the gene responsible for producing the EGFR protein mutates, it can become a biomarker linked to the development and progression of certain cancers.
The presence of an EGFR mutation provides specific information about a cancer, guiding medical professionals in their diagnosis and management of the condition. This allows for a more detailed diagnostic picture beyond a general disease classification. Identifying these specific genetic markers has opened a new chapter in diagnostics and treatment strategies.
The Function of EGFR in Cancer
In a healthy body, the EGFR protein functions like a controlled switch for cell division. When a growth factor molecule binds to the receptor on the cell’s surface, it activates a signaling pathway inside the cell, instructing it to grow and divide. This process is tightly regulated, ensuring that cells multiply only when needed for tissue maintenance and repair. The system has mechanisms to turn the switch “off” once the need for new cells has been met.
In certain cancers, mutations in the EGFR gene disrupt this regulatory system. These genetic errors can cause the EGFR protein to become structurally altered, jamming the switch in the “on” position. This leads to constant, unregulated signaling that tells the cell to divide continuously. This uncontrolled growth drives the formation and spread of tumors.
This mechanism is most associated with non-small cell lung cancer (NSCLC), where EGFR mutations are a common driver of the disease. They are prevalent in lung adenocarcinoma, a subtype of NSCLC, and are more frequently seen in certain demographics, including women and individuals who have never smoked. Similar EGFR-related growth signals have been identified in other cancers, such as colorectal cancer, though the specific mutations and their implications can differ.
Testing for EGFR Mutations
To determine if a cancer is driven by EGFR mutations, doctors analyze the tumor’s genetic makeup through biomarker testing. This step is important for creating a complete diagnosis and informing the treatment plan. The results of this testing will show whether the tumor is “EGFR-positive,” meaning it harbors one of the specific mutations known to drive cancer growth.
The most established method for this analysis is a tissue biopsy. During this procedure, a small sample of the tumor is surgically removed. This tissue is then sent to a laboratory for molecular testing to sequence the EGFR gene and identify any mutations. A tissue biopsy is a highly accurate method for obtaining a detailed genetic profile of the tumor.
A less invasive alternative is the liquid biopsy. This technique involves a simple blood draw to detect and analyze circulating tumor DNA (ctDNA), which are fragments of genetic material shed by cancer cells into the bloodstream. This method is useful for monitoring how a cancer is responding to treatment or for situations where a tissue biopsy is not feasible. A liquid biopsy offers a non-invasive way to gather genetic information and track changes over time.
Targeted Therapies for EGFR-Mutated Cancers
Identifying an EGFR mutation allows for a specialized treatment approach known as targeted therapy. Unlike traditional chemotherapy, which affects all rapidly dividing cells, targeted therapies act specifically on the cancer cells that have the EGFR mutation. These drugs, called EGFR Tyrosine Kinase Inhibitors (TKIs), work by blocking the part of the faulty EGFR protein responsible for sending growth signals. By inhibiting this signal, TKIs turn off the switch that drives cancer proliferation.
The effectiveness of these therapies depends on the specific type of EGFR mutation present. Certain mutations, referred to as “sensitizing” mutations, are particularly responsive to TKIs. The most common of these include deletions in a region of the EGFR gene known as exon 19 and a specific point mutation called L858R. These two types account for the majority of EGFR mutations that respond well to initial treatment.
The development of EGFR TKIs has progressed through several generations. First-generation drugs like gefitinib and erlotinib were the initial breakthroughs in this class. Second-generation inhibitors followed, aiming for broader effects. Third-generation TKIs, such as osimertinib, have been developed to target both the initial sensitizing mutations and specific resistance mutations that can develop later.
Understanding Acquired Resistance
A significant challenge in treating EGFR-positive cancers is the development of acquired resistance. Over time, a tumor that was once controlled by a targeted therapy can evolve and develop new mutations that render the initial drug ineffective. This happens because the cancer cells are under selective pressure from the treatment, and any cells that develop a new mutation allowing them to bypass the drug’s blocking action will multiply.
This process means the cancer begins to grow again despite ongoing treatment. One of the most common mechanisms of acquired resistance to first- and second-generation EGFR TKIs is the emergence of a secondary mutation known as T790M. This change in the EGFR gene alters the protein so that the earlier drugs can no longer bind to it effectively, allowing the growth signals to resume.
When a patient’s cancer shows signs of progressing after successful treatment, doctors may suspect acquired resistance. Further testing is necessary to confirm this and identify the specific genetic cause. A liquid biopsy is often used in this scenario to detect new resistance mutations like T790M. Identifying the mechanism of resistance allows oncologists to switch to a different therapy, such as a newer-generation inhibitor designed to overcome that resistance.