egfr

An exon 19 deletion removes a few amino acids from the EGFR kinase and leaves it switched on. With L858R it makes up about 85 percent of EGFR-mutant lung cancer and is the classic gate for osimertinib and the other EGFR inhibitors.

Exon 20 insertions add amino acids after the C-helix of EGFR and make the kinase resistant to the usual EGFR tablets. They account for about a tenth of EGFR mutations and have their own drugs: amivantamab with chemotherapy and sunvozertinib.

L858R is a single letter change in exon 21 of EGFR that keeps the kinase active. It is the second commonest sensitising mutation and shares every EGFR inhibitor label with the exon 19 deletion.

T790M is the gatekeeper mutation that lung cancers acquire to escape first- and second-generation EGFR inhibitors. Finding it, in tissue or blood, is the historic gate for osimertinib after an earlier EGFR drug.