Epidermal Growth Factor Receptor (EGFR) is a transmembrane tyrosine kinase receptor regulating cell proliferation, survival, and differentiation. Mutations in the *EGFR* gene, particularly exon 19 deletions and L858R substitutions, drive constitutive kinase activation, promoting oncogenesis in non-small cell lung cancer (NSCLC) and other malignancies. Targeting mutant EGFR has become a cornerstone of precision oncology.
EGFR mutant-specific antibodies are critical tools for both diagnostic and therapeutic applications. Therapeutically, monoclonal antibodies (e.g., cetuximab, panitumumab) bind EGFR’s extracellular domain to block ligand-induced signaling. However, these antibodies primarily target wild-type EGFR and show limited efficacy against tumors harboring kinase domain mutations. Tyrosine kinase inhibitors (TKIs), such as osimertinib, more directly inhibit mutant EGFR kinase activity and remain first-line therapies.
Diagnostically, mutation-selective antibodies (e.g., EGFR exon 19 deletion-specific clones) enable immunohistochemical detection of mutant EGFR in tumor samples, aiding rapid clinical decision-making where molecular testing is unavailable. Recent advancements include bispecific antibodies and antibody-drug conjugates designed to enhance tumor specificity and overcome TKI resistance mechanisms like T790M or C797S mutations.
Research continues to address challenges such as tumor heterogeneity, resistance, and on-target toxicity. The integration of mutant EGFR antibodies with next-generation sequencing and combination therapies underscores their evolving role in personalized cancer treatment.