Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. A specific genetic alteration, the epidermal growth factor receptor (EGFR) mutation, can be present in some tumor cells. This mutation changes the DNA of cancer cells, influencing their growth and division. Understanding this genetic change is important because it distinguishes a subset of NSCLC that responds differently to certain treatments.
Understanding EGFR and Non-Small Cell Lung Cancer
Non-small cell lung cancer is a broad term for several types of lung cancer, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. It typically grows and spreads more slowly than small cell lung cancer. NSCLC begins when lung cells grow out of control, forming tumors.
The Epidermal Growth Factor Receptor (EGFR) is a protein on the surface of cells, including lung cells. Its normal function is to receive signals that tell cells to grow and divide. When a growth factor binds to EGFR, it activates a pathway promoting cell growth and survival.
An EGFR mutation is an alteration in the gene that produces the EGFR protein. In lung cancer, these mutations lead to an overactive EGFR protein that continuously sends growth signals. This uncontrolled signaling drives the growth of cancer cells, contributing to tumor formation. This mutation transforms the cancer into a distinct subtype, making it amenable to targeted therapies.
Identifying the EGFR Mutation
Testing for the EGFR mutation is a routine step in managing NSCLC, as its presence influences treatment decisions. Identifying this alteration allows oncologists to select therapies designed to target the mutated protein, offering a more personalized approach. This testing helps determine if a patient’s cancer will respond to certain medications.
A common method for identifying the EGFR mutation is a tissue biopsy, where a small tumor sample is removed. This sample is analyzed in a laboratory to detect genetic changes within the EGFR gene. Pathologists examine the DNA to pinpoint mutations, such as exon 19 deletions or the L858R point mutation, which are the most frequently observed EGFR alterations.
Another technique is a liquid biopsy, which analyzes a blood sample for circulating tumor DNA (ctDNA). Cancer cells shed DNA fragments into the bloodstream, which can be collected and tested for EGFR mutations. Liquid biopsies offer a less invasive alternative to tissue biopsies, especially when a tissue sample is difficult to obtain or insufficient. Both methods identify the cancer’s genetic blueprint, guiding the selection of targeted therapies.
Targeted Therapies for EGFR Mutated NSCLC
Targeted therapy is a specialized approach to treating cancer, focusing on specific molecules that drive cancer cell growth, like the mutated EGFR protein. Unlike traditional chemotherapy, which broadly attacks rapidly dividing cells, targeted therapies inhibit the abnormal activity caused by the EGFR mutation. This precision often leads to fewer side effects and a better response in patients whose tumors harbor these genetic changes.
EGFR Tyrosine Kinase Inhibitors (TKIs) are the main type of targeted therapy for EGFR-mutated NSCLC. These medications block the activity of the mutated EGFR protein, interrupting the continuous growth signals that fuel cancer cell growth. EGFR TKIs have progressed through different generations, each offering advancements in efficacy and managing resistance.
First-generation EGFR TKIs, such as erlotinib and gefitinib, were the earliest drugs to inhibit the EGFR pathway. They block the active site of the mutated EGFR protein, leading to tumor shrinkage in many patients with common EGFR mutations like exon 19 deletions and L858R. Second-generation TKIs, including afatinib and dacomitinib, offer broader and more irreversible inhibition of the EGFR protein, providing more sustained responses.
The third-generation TKI, osimertinib, represents a significant advancement because it targets the T790M mutation, a common mechanism of acquired resistance to first- and second-generation TKIs. Osimertinib is often used as a first-line treatment for certain EGFR mutations and for patients who develop the T790M mutation after initial therapy. The selection of a TKI depends on the type of EGFR mutation identified and prior treatment history. Common side effects include skin rash and diarrhea, which are generally manageable.
Ongoing Management and Monitoring
Ongoing management for EGFR-mutated NSCLC involves regular follow-up to assess treatment effectiveness and address disease changes. This includes periodic imaging, such as CT scans, to monitor tumor size and detect cancer progression. These evaluations help determine if the current targeted therapy is working.
Despite initial success with targeted therapies, cancer cells can develop new mutations that make them resistant to the medication. This phenomenon, known as acquired resistance, can lead to the cancer growing again. When resistance is suspected, further testing, such as a re-biopsy or another liquid biopsy, may be performed to identify new mutations, like the T790M mutation, which drives resistance to first- and second-generation TKIs.
Identifying new resistance mutations guides subsequent treatment decisions, leading to a switch to a different targeted therapy, such as a third-generation TKI like osimertinib. Supportive care is an important component of long-term management, focusing on alleviating treatment side effects and improving quality of life. This comprehensive approach often involves a multidisciplinary team, including oncologists, nurses, and other specialists, providing continuous care and adapting treatment strategies as the disease evolves.