An EGFR exon 19 deletion is a specific genetic alteration found within some cancer cells, particularly in non-small cell lung cancer (NSCLC). This term describes a situation where a small portion of the genetic instructions in a cancer cell is missing. Identifying this mutation allows doctors to understand what drives the tumor’s growth, which opens the door to treatments designed to counteract this specific genetic change.
The Science of the EGFR Mutation
To understand this mutation, it helps to break down the term “EGFR exon 19 deletion.” EGFR stands for Epidermal Growth Factor Receptor, a protein on the surface of cells. This protein’s normal function is to receive signals that tell the cell when to grow and divide in a controlled manner, a process necessary for tissue maintenance and repair. The instructions for building this protein are contained within the EGFR gene.
A gene’s instructions are organized into sections called exons, which contain the protein-building code. The EGFR gene has multiple exons, and a deletion in exon 19 means a specific piece of the genetic code is missing from this section. This seemingly small error has significant consequences for the protein’s function.
The missing genetic material causes the resulting EGFR protein to be malformed. This altered protein gets stuck in a permanently “on” state, even without receiving external signals to grow. This is often compared to a car’s gas pedal being stuck down, causing the cell to receive nonstop signals to grow and divide, leading to the uncontrolled proliferation that defines cancer.
Diagnosis and Testing
The process of identifying an EGFR exon 19 deletion begins after a cancer diagnosis is confirmed. The initial step is a biopsy, where a small sample of the tumor is removed and examined by a pathologist to confirm the type of cancer, such as NSCLC. This is followed by a specialized analysis of the cancer cells’ genetic makeup.
This step, called molecular or genomic testing, is performed on the tumor tissue to search for specific genetic mutations known to drive cancer growth. The goal is to create a molecular profile of the tumor, which includes looking for alterations like the EGFR exon 19 deletion. This information helps plan the most effective treatment course.
If a tissue biopsy is not possible or the sample is insufficient, a liquid biopsy may be used. This less invasive test analyzes a patient’s blood to detect circulating tumor DNA (ctDNA) shed by the tumor. This method can also identify the EGFR exon 19 deletion and other mutations, helping to guide treatment decisions without a surgical procedure.
Targeted Therapy Treatments
Discovering an EGFR exon 19 deletion allows doctors to use a class of drugs known as targeted therapies. Unlike traditional chemotherapy, which affects all rapidly dividing cells, targeted therapies are designed to act on the specific molecular abnormalities that drive cancer. The primary treatment involves drugs called EGFR Tyrosine Kinase Inhibitors, or TKIs.
TKIs work by entering the cancer cell and binding to the part of the EGFR protein that is stuck in the “on” position. This action blocks the protein’s ability to send continuous growth signals, thereby slowing or stopping the cancer’s proliferation. For patients with the exon 19 deletion, these drugs can be very effective.
Several EGFR TKIs are approved by the U.S. Food and Drug Administration (FDA) for treating this type of lung cancer. Common TKIs used include:
- Osimertinib (Tagrisso), which is frequently used as a first-line treatment
- Gefitinib (Iressa)
- Erlotinib (Tarceva)
- Afatinib (Gilotrif)
The choice of TKI depends on factors like the patient’s overall health and cancer characteristics, but all are designed to inhibit the faulty EGFR pathway.
Prognosis and Treatment Response
For patients with non-small cell lung cancer, the presence of an EGFR exon 19 deletion indicates a more favorable prognosis compared to patients without this mutation when treated with EGFR TKIs. These targeted drugs have significantly changed the outlook for this subgroup of patients. The mutation makes the cancer cells vulnerable to the specific mechanism of TKIs, leading to better outcomes.
Treatment response to TKIs in this population is high, with a large percentage of patients experiencing tumor shrinkage. Studies show that patients with an exon 19 deletion have longer progression-free survival (PFS) when treated with TKIs compared to those with other EGFR mutations. PFS is the length of time a patient lives with the disease without it worsening.
This positive response is a direct result of the targeted nature of the therapy. By shutting down the primary driver of the cancer’s growth, TKIs can control the disease for extended periods. While not a cure, the high response rates have helped manage EGFR-mutated NSCLC as a more chronic condition for many patients.
Acquired Resistance and Future Steps
A challenge in the long-term management of EGFR-mutated lung cancer is the development of acquired resistance. Over time, cancer cells can evolve and develop new mutations that allow them to bypass the effects of the initial TKI treatment. This causes the therapy to become less effective, and most patients eventually see their disease progress.
One of the most common mechanisms of resistance is the development of a secondary mutation in the EGFR gene known as T790M. This new mutation alters the EGFR protein, preventing first-generation TKIs from binding to it effectively, which allows the cancer cells to resume their uncontrolled growth. The emergence of the T790M mutation accounts for about half of all cases of acquired resistance to earlier TKIs.
When resistance is suspected, another biopsy is performed to identify the new resistance mechanism. If the T790M mutation is found, a patient may be switched to a different TKI designed to target it, such as osimertinib. In cases where other resistance mechanisms are identified or if no specific mutation is found, other treatment options are considered, including chemotherapy, radiation, or enrollment in clinical trials.