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When a cancer becomes resistant to a targeted pill, it often does so by changing the exact spot where the drug binds: a 'gatekeeper' or 'solvent-front' mutation. Next-generation drugs are designed to fit around these changes.
Gatekeeper mutations (EGFR T790M, ABL T315I, KIT T670I) alter a residue at the entrance to the ATP pocket; solvent-front mutations (ALK G1202R, ROS1 G2032R, NTRK G595R) change the drug's contact surface; compound mutations stack two or more changes and defeat successive drug generations. Each generation of inhibitor answers the last: osimertinib for T790M, lorlatinib and neladalkib for G1202R, ponatinib and asciminib for T315I, repotrectinib for G2032R. Re-biopsy or ctDNA at progression identifies the mutation and guides the switch; off-target bypass (MET amplification, histologic transformation) is the other main route.
In plain words · A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
Showing the target this term concerns: EGFR.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
Shares EGFR T790M, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), Cell-free DNA (cfDNA), Drug resistance (primary and acquired).
Shares EGFR T790M, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), Drug resistance (primary and acquired), Osimertinib.
Shares ROS1, NTRK fusion-positive non-small-cell lung cancer, RET fusion-positive non-small-cell lung cancer, ROS1-positive non-small-cell lung cancer.
Shares EGFR T790M, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), ROS1, Cell-free DNA (cfDNA).
Shares EGFR T790M, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), Drug resistance (primary and acquired), EGFR.
Shares EGFR T790M, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), Drug resistance (primary and acquired), EGFR.
Shares EGFR T790M, EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M), Drug resistance (primary and acquired), EGFR.
Shares NTRK fusion-positive non-small-cell lung cancer, RET fusion-positive non-small-cell lung cancer, ROS1-positive non-small-cell lung cancer.