Epidermal growth factor receptor C797S mutation (EGFR C797S)

The **epidermal growth factor receptor C797S mutation** refers specifically to a substitution at codon 797 in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), where cysteine is replaced by serine. This alteration confers high-level resistance to third-generation covalent EGFR tyrosine kinase inhibitors such as osimertinib, which require covalent bonding with cysteine at position 797 for their inhibitory effect. The presence of this mutation does not significantly alter overall structure or function but prevents formation of a critical covalent bond with these drugs, rendering them ineffective. As a result, patients whose tumors acquire this secondary/tertiary resistance mechanism have limited treatment options. Research has focused on developing next-generation allosteric and non-covalent inhibitors that can overcome this resistance by selectively targeting the altered binding site without relying on interaction with residue 797. The detection of the **EGFR C797S** variant serves as an important biomarker for acquired drug resistance in cancers such as non–small cell lung cancer and guides subsequent therapeutic strategies[1][2][3][4].

Other names

EGFR C797SEpidermal growth factor receptor cysteine 797 serine mutationEGFR exon 20 C797S mutation

Inhibitors targeting this mutant act by selectively binding to the mutated kinase domain and inhibiting its activity, often through non-covalent or allosteric mechanisms due to loss of covalent binding at position 797[4][1].