Epidermal growth factor receptor (EGFR) S768I mutant (EGFR S768I)

The Epidermal growth factor receptor (EGFR) S768I mutant is a specific oncogenic variant of the EGFR protein, a transmembrane receptor tyrosine kinase belonging to the ErbB family (oncokb.org). This mutation, located in exon 20, involves a substitution of serine with isoleucine at codon 768 and is classified as an uncommon or minor mutation, occurring in approximately 1-2% of EGFR-mutant non-small cell lung cancers (NSCLC) (nih.gov). The S768I mutation leads to constitutive activation of the receptor's kinase domain, triggering downstream signaling pathways such as PI3K/AKT and MAPK/ERK that drive uncontrolled cell growth and survival (nih.gov, mdpi.com). Clinically, tumors harboring this mutation show varying sensitivity to tyrosine kinase inhibitors (TKIs); they are generally highly sensitive to second-generation irreversible inhibitors like afatinib, while showing moderate or variable responses to first-generation (erlotinib, gefitinib) and third-generation (osimertinib) agents (oncokb.org, nih.gov). The presence of S768I often occurs in combination with other sensitizing mutations, and its detection via molecular profiling is crucial for tailoring effective therapeutic strategies (nih.gov). Management of patients with this mutation also involves monitoring for acquired resistance mechanisms, most notably the T790M secondary mutation (nih.gov). Overall, the S768I variant represents a distinct molecular subset of lung cancer that requires specific clinical consideration for optimal management.

Other names

ErbB1 S768IHER1 S768IEGFR exon 20 S768I mutationp.Ser768IleEGFR S768I mutation

Tyrosine kinase inhibition through reversible or irreversible binding to the ATP-binding site of the EGFR kinase domain (nih.gov, mdpi.com).