Epidermal growth factor receptor (EGFR) exon 19 deletion mutant (EGFR Del19)

The Epidermal growth factor receptor (EGFR) exon 19 deletion mutant is a primary oncogenic driver in non-small cell lung cancer (NSCLC), particularly in lung adenocarcinomas [1, 10]. This mutation involves an in-frame deletion within the kinase domain of the EGFR protein, which leads to constitutive activation of downstream signaling pathways such as PI3K/AKT and MAPK/ERK [1, 16]. These pathways promote uncontrolled cell proliferation, survival, and metastasis [7, 16]. The Del19 mutation is one of the most common sensitizing mutations, accounting for approximately 45-50% of all EGFR mutations in NSCLC patients [9, 18]. It is highly responsive to treatment with EGFR tyrosine kinase inhibitors (TKIs), including first-generation (gefitinib, erlotinib), second-generation (afatinib, dacomitinib), and third-generation (osimertinib, lazertinib) agents [1, 13]. Despite high initial response rates, patients typically develop acquired resistance, often through secondary mutations like T790M or C797S, or bypass signaling mechanisms like MET amplification [14, 19]. Clinical management involves regular monitoring through tissue or liquid biopsies to detect these resistance markers and adjust therapy accordingly [15, 21].

Other names

Exon 19 deletionDel19Ex19DelΔ746-750E746_A750delEGFR-activating mutationErbB1 exon 19 deletion

Tyrosine kinase inhibition, Irreversible covalent binding, Competitive ATP inhibition