EGFR: Oncogenic Signaling, Mutations, and Targeted Therapy
Exploring the critical role of Epidermal Growth Factor Receptor in precision oncology.
Epidermal growth factor receptor (EGFR) is a critical cell-surface receptor tyrosine kinase involved in the regulation of cell proliferation, differentiation, and survival.
Dysregulation of EGFR signaling—most commonly through genetic mutations or overexpression—plays a central role in the development and progression of multiple malignancies, making it a cornerstone of modern cancer research.
Figure 1: EGFR Structural Domains and Activation
Structural Architecture
EGFR is a single-pass transmembrane receptor composed of three major functional domains:
Extracellular Ligand-binding domain for EGF/TGF-α
Transmembrane Hydrophobic region crossing the membrane
Intracellular Tyrosine kinase domain for signaling
I. EGFR and Its Role in Cancer
• Oncogenic Mechanisms
In cancers such as non-small cell lung cancer (NSCLC), activating mutations in the EGFR gene result in constitutive receptor activation, leading to uncontrolled tumor cell proliferation and survival.
• Downstream Signaling Pathways
Activated EGFR transduces oncogenic signals through multiple intracellular cascades, most notably:
RAS–RAF–MAPK: Directs cell cycle progression and growth.
PI3K–AKT: Promotes resistance to apoptosis and metabolic reprogramming.
II. EGFR-Targeted Therapeutic Strategies
Advances in molecular oncology have enabled the development of targeted therapies designed to selectively inhibit aberrant EGFR signaling.
Strategy
Mechanism & Examples
Small-molecule TKIs
Gefitinib, Erlotinib: Competitively inhibit the kinase domain in EGFR-mutant NSCLC.
Monoclonal Antibodies
Cetuximab: Targets the extracellular domain, commonly used in colorectal cancer.
Overcoming Resistance
Osimertinib: A 3rd-generation TKI designed to target the T790M mutation.
By teamBiofargo
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