Determination of EGFR gene mutation from biopsy sample of tumor tissue by PCR method
EGFR (Epidermal Growth Factor Receptor) is a receptor for epidermal growth factor, playing a crucial role in regulating cell growth, division, and survival. It is an important target for targeted therapy in certain types of cancer. Mutations in the EGFR gene can lead to the activation of signaling pathways, contributing to tumor growth and metastasis. Testing for EGFR mutations helps in personalized therapy and selecting effective treatment methods.
What is EGFR?
EGFR (Epidermal Growth Factor Receptor) is a membrane receptor that is activated upon binding with the epidermal growth factor (EGF).
Once bound to EGF, the receptor activates signaling pathways such as MAPK (Mitogen-Activated Protein Kinase) and PI3K (Phosphoinositide 3-Kinase), which stimulate cell proliferation and survival.
Under normal conditions, this process is tightly regulated, but mutations in the EGFR gene can lead to uncontrolled cell growth and cancer development.
Role of EGFR in Cancer
Mutations in EGFR can lead to the activation of signaling pathways even in the absence of external signals, promoting tumor development. These mutations are most commonly found in diseases such as lung cancer, head and neck cancer, and certain breast cancers.
Lung Cancer
- In non-small cell lung cancer (NSCLC) and small cell lung cancer, EGFR mutations are found in 10-20% of patients, especially in non-smoking women with adenocarcinoma.
EGFR mutations make the tumor sensitive to EGFR inhibitors, such as gefitinib, erlotinib, afatinib, and others.
Head and Neck Cancer
- EGFR mutations can also occur in squamous cell carcinoma of the head and neck, where this receptor plays an active role in tumor progression.
Breast Cancer
- In some cases of breast cancer, there is increased EGFR expression, which may be associated with a more aggressive course of the disease.
Types of EGFR Mutations
Mutations in the EGFR gene can vary:
Activating mutations - These are most commonly found in exons 18, 19, 20, and 21. These mutations lead to receptor hyperactivation, causing enhanced cell proliferation.
- T790M mutation - This mutation is often associated with resistance to EGFR inhibitor therapy.
- EGFR amplification - This refers to an increase in the number of EGFR receptors in the cell, which is also linked to aggressive tumor growth.
Prognosis and Treatment
Lung Cancer
- Patients with EGFR mutations typically respond better to EGFR inhibitors (e.g., gefitinib, erlotinib, osimertinib) than to traditional chemotherapy. This makes EGFR mutation testing important for selecting targeted therapy.
- The T790M mutation can indicate the development of resistance to initial treatment with EGFR inhibitors, and in such cases, second-generation inhibitors, such as osimertinib, may be considered.
Head and Neck Cancer
- Increased EGFR expression in squamous cell carcinoma of the head and neck may lead to treatment with cetuximab, a monoclonal antibody targeting EGFR.
Breast Cancer
- Increased EGFR expression in breast cancer tumors may indicate an aggressive disease course and may require the use of targeted therapies against EGFR