Epidermal growth factor receptor (EGFR) mutants (EGFR)

The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase that plays a critical role in regulating cell signaling pathways involved in growth, proliferation, and survival [2, 16]. Mutations in the EGFR gene, particularly those affecting the intracellular kinase domain, lead to constitutive activation of the receptor and are major drivers of oncogenesis in several malignancies, most notably non-small cell lung cancer (NSCLC) and glioblastoma [4, 10]. These mutations are broadly categorized into sensitizing mutations, such as exon 19 deletions and the L858R point mutation, which confer sensitivity to first-generation tyrosine kinase inhibitors (TKIs), and resistance mutations like T790M and C797S that emerge during treatment [7, 9]. Therapeutic intervention involves small-molecule TKIs that compete with ATP for binding to the kinase domain, as well as monoclonal antibodies and bispecific antibodies that target the extracellular portion of the receptor [3, 12, 21]. While targeted therapies have significantly improved patient outcomes, the inevitable development of acquired resistance through secondary mutations remains a primary therapeutic challenge [5, 20]. Consequently, the management of EGFR-mutant cancers requires continuous monitoring of mutational status and the use of successive generations of inhibitors designed to overcome specific resistance mechanisms [14, 15].

Other names

ErbB1HER1Proto-oncogene c-ErbB-1mEGFRCell proliferation-inducing protein 61

Tyrosine kinase inhibition via competitive ATP binding or irreversible covalent modification; extracellular domain blockade via monoclonal antibodies; bispecific targeting of EGFR and MET