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Drug Target Encyclopedia Series (6) — EGFR
Release Time：
2025-12-05 10:28
The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase of the ErbB family, widely expressed in epithelial tissues. Upon ligand binding, EGFR activates downstream signaling pathways such as MAPK, PI3K/AKT, and JAK/STAT—governing key cellular processes including proliferation, survival, differentiation, and migration.
Dysregulation of EGFR is implicated in a broad range of cancers, including non-small cell lung cancer (NSCLC), colorectal cancer, glioblastoma, and head and neck squamous cell carcinoma. Mutations, amplifications, and overexpression of EGFR can drive tumor growth and resistance to therapy.
EGFR has become a cornerstone target in precision oncology, with a diverse portfolio of therapeutic strategies:
- Small molecule EGFR tyrosine kinase inhibitors (TKIs) – such as gefitinib, erlotinib, osimertinib – designed to block aberrant kinase activity, especially in NSCLC with EGFR mutations.
- Monoclonal antibodies – like cetuximab and panitumumab – that inhibit ligand binding and receptor dimerization.
- Antibody-drug conjugates (ADCs) – delivering cytotoxic payloads directly to EGFR-expressing tumor cells.
- Bispecific antibodies and CAR-T therapies – in development to expand EGFR targeting into new modalities.
Resistance mechanisms—including secondary mutations (e.g., T790M, C797S), MET amplification, and bypass signaling—continue to challenge long-term efficacy, driving innovation in next-generation inhibitors and combination strategies.
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