Epidermal growth factor receptor (EGFR) is a protein that resides on the cell surface and is involved in various cellular processes, including cell growth and division. In recent years, EGFR has been recognized as a critical player in the development and progression of lung cancer. This article aims to explore the role of EGFR in lung cancer in detail.
EGFR and Its Role in Cell Function
EGFR is a member of the ErbB family of receptors, a group of four closely related receptor tyrosine kinases. Under normal physiological conditions, EGFR plays a crucial role in cell signaling pathways that regulate cell growth, proliferation, differentiation, and survival. It does so by interacting with specific ligands, such as epidermal growth factor (EGF), leading to the activation of downstream signaling cascades.
EGFR in Lung Cancer
In the context of lung cancer, particularly non-small cell lung cancer (NSCLC), the role of EGFR becomes notably complex. Alterations in the EGFR gene, such as mutations or overexpression, can lead to uncontrolled activation of the receptor, promoting tumor growth and progression. The most common EGFR mutations, exon 19 deletions and an exon 21 L858R substitution, result in constitutive activation of the EGFR tyrosine kinase, driving cancer cell proliferation, survival, and migration.
EGFR as a Therapeutic Target
The central role of EGFR in lung cancer pathogenesis has made it an attractive target for therapeutic intervention. EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib, and afatinib, have been developed to block the activity of the EGFR tyrosine kinase, thereby inhibiting the downstream signaling pathways involved in tumor growth and survival. These targeted therapies have shown significant clinical benefits in NSCLC patients harboring activating EGFR mutations. However, resistance to EGFR TKIs inevitably develops, often due to additional mutations in the EGFR gene, such as the T790M mutation. This challenge has led to the development of third-generation EGFR TKIs, like osimertinib, which can effectively target T790M-positive tumors.