The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor that plays a critical role in regulating cell proliferation, survival, differentiation, and migration. Overexpression or hyperactivation of EGFR, often due to mutations or gene amplification, is implicated in various cancers, including non-small cell lung cancer (NSCLC), colorectal cancer, and head and neck cancers. This makes EGFR a key therapeutic target in oncology.
EGFR-targeted antibodies are a class of biologic drugs designed to inhibit EGFR signaling. These include monoclonal antibodies (mAbs) such as cetuximab and panitumumab, which bind to the extracellular domain of EGFR, blocking ligand-induced activation and downstream signaling pathways like RAS/RAF/MEK/ERK and PI3K/AKT/mTOR. By doing so, they suppress tumor growth, angiogenesis, and metastasis. Cetuximab, a chimeric IgG1 antibody, also induces antibody-dependent cellular cytotoxicity (ADCC).
Clinically, EGFR antibodies are used alone or combined with chemotherapy/radiotherapy. Cetuximab is approved for metastatic colorectal cancer (wild-type KRAS) and head and neck cancers, while panitumumab targets colorectal cancer. However, resistance mechanisms, such as KRAS mutations or EGFR extracellular domain alterations, limit efficacy. Research continues to develop next-generation antibodies, bispecific constructs, and combination therapies to overcome resistance and improve outcomes. Overall, EGFR antibodies represent a cornerstone of precision oncology, exemplifying targeted therapy's potential in personalized cancer treatment.