Epidermal growth factor receptor T790M mutant (EGFR T790M) (EGFR T790M)

The **epidermal growth factor receptor (EGFR) T790M mutant** is a specific form of the human EGFR protein where threonine at position 790 in its tyrosine kinase domain is replaced by methionine. This single-point mutation is a well-characterized mechanism of acquired resistance to first-generation EGFR tyrosine kinase inhibitors used in treating non-small cell lung cancer. The substitution increases ATP affinity at the binding site while reducing inhibitor binding efficiency, leading to treatment failure with drugs like gefitinib or erlotinib. Third-generation TKIs such as osimertinib have been developed specifically to overcome this resistance by selectively inhibiting both activating mutations and the resistant T790M variant while sparing wild-type receptors—resulting in improved clinical outcomes for patients whose tumors harbor this mutation.

Other names

EGFR T790M mutationEpidermal growth factor receptor threonine 790 to methionine mutantEGFR tyrosine kinase domain T790M

Drugs targeting the EGFR T790M mutant act primarily as **tyrosine kinase inhibitors**. Third-generation inhibitors such as osimertinib and rociletinib are designed to selectively and irreversibly bind the mutated ATP-binding site of the receptor (often via covalent bonding with Cys797), overcoming resistance conferred by the T790M mutation. Some agents use reversible or allosteric inhibition strategies.