Epidermal growth factor receptor (EGFR) mutant (EGFR)

The Epidermal Growth Factor Receptor (EGFR) is a transmembrane receptor tyrosine kinase that plays a critical role in cell signaling pathways governing growth and survival [1.2.1, 1.3.1]. Mutations within the intracellular kinase domain, particularly in exons 18 through 21, lead to constitutive activation of the receptor, driving oncogenesis in several cancers, most notably non-small cell lung cancer (NSCLC) [1.3.2, 1.4.2]. These mutant forms, such as the L858R point mutation and exon 19 deletions, are highly sensitive to targeted tyrosine kinase inhibitors (TKIs) [1.1.3, 1.4.4]. However, clinical efficacy is often limited by the development of acquired resistance mutations, such as the T790M gatekeeper mutation or the C797S mutation, which interfere with drug binding [1.1.3, 1.3.2]. Modern therapeutic strategies involve third-generation TKIs like osimertinib, which covalently bind to the mutant kinase domain while sparing wild-type EGFR to reduce toxicity [1.1.3, 1.3.1]. Additionally, exon 20 insertion mutations represent a distinct class of alterations that require specific inhibitors like mobocertinib or bispecific antibodies like amivantamab [1.4.3]. The management of EGFR-mutant cancers relies heavily on molecular profiling to identify specific mutations and tailor treatment accordingly [1.4.3, 1.4.5]. Ongoing research continues to explore fourth-generation TKIs and combination therapies to overcome complex resistance patterns [1.1.4, 1.3.1].

Other names

HER1ERBB1Proto-oncogene c-ErbB-1Receptor tyrosine kinase ErbB-1

Inhibition of the intracellular tyrosine kinase domain by competing with ATP binding, leading to the suppression of downstream signaling pathways such as Ras/Raf/MEK/ERK and PI3K/Akt [1.1.2, 1.1.3].