Epidermal growth factor receptor exon 19 deletion (EGFR exon 19del)

Epidermal growth factor receptor exon 19 deletion refers to a group of activating mutations within exon 19 of the *EGFR* gene. These deletions typically remove several amino acids from positions E746 to D761 in the tyrosine kinase domain—most commonly E746-A750—and result in constitutive activation of the receptor’s kinase activity. This leads to increased autophosphorylation and persistent activation of downstream signaling pathways such as AKT and STAT, promoting uncontrolled cell proliferation and survival[1][4]. EGFR exon 19 deletions are among the most frequent driver mutations found in non-small cell lung cancer (NSCLC), especially adenocarcinoma subtypes. They predict sensitivity to targeted therapy with small-molecule tyrosine kinase inhibitors (TKIs) like erlotinib, gefitinib, afatinib, and osimertinib[2][3][5]. There are many molecular subtypes based on precise breakpoints; some rare variants may have different responses or prognoses compared with common forms like delE746-A750[1][2]. Testing for these deletions is standard practice for guiding treatment decisions in advanced NSCLC. However, resistance inevitably develops—often through secondary mutations such as T790M or C797S—which can limit long-term efficacy of TKIs[5]. The complexity and diversity of these deletions present diagnostic challenges but remain central targets for precision oncology approaches in lung cancer management.

Other names

EGFR exon 19 deletionEGFR 19delEpidermal growth factor receptor E746-A750 deletion (for the most common subtype)EGFR ΔE746-A750Epidermal growth factor receptor delE746-A750

Drugs targeting this molecule act as tyrosine kinase inhibitors. They bind to the ATP-binding site of the mutant EGFR protein, inhibiting its autophosphorylation and downstream signaling pathways that drive tumor cell proliferation and survival[4][5].