Epidermal Growth Factor Receptor T790M Mutant (EGFR T790M)

The Epidermal Growth Factor Receptor (EGFR) T790M mutant refers to a specific point mutation in the EGFR gene, where threonine (T) at position 790 is replaced by methionine (M). This mutation occurs within exon 20 of the EGFR tyrosine kinase domain. The T790M mutation is most frequently associated with acquired resistance in non-small cell lung cancer (NSCLC) patients who initially respond to EGFR-TKI therapy but later relapse. Third-generation irreversible covalent inhibitors—most notably osimertinib—are specifically designed to overcome T790M-mediated resistance.

Other names

EGFR Thr790MetEGFR T790M MutationT790M mutationT790M EGFR

The T790M mutation increases EGFR's affinity for ATP, leading to competitive resistance against reversible tyrosine kinase inhibitors (TKIs). Osimertinib, an irreversible third-generation TKI, overcomes this resistance by covalently binding to EGFR, even in the presence of the T790M mutation.