Osimertinib is a third-generation EGFR tyrosine kinase inhibitor. EGFR is a receptor involved in cellular signaling, growth and survival. Certain EGFR mutations can make lung cancer cells dependent on abnormal EGFR signaling.
Osimertinib binds irreversibly to selected mutant forms of EGFR and inhibits their kinase activity. The medicine has activity against EGFR exon 19 deletions, exon 21 L858R mutations and the T790M resistance mutation.
Simple explanation
Some NSCLC tumors contain EGFR changes that cause persistent growth signals. Osimertinib acts like a molecular switch-off mechanism for relevant mutant EGFR signaling.
T790M
T790M is a resistance mutation that can emerge after treatment with earlier EGFR tyrosine kinase inhibitors. Osimertinib was specifically developed to inhibit mutant EGFR including T790M.
Selectivity
Osimertinib has greater activity against certain mutant EGFR forms than wild-type EGFR. Its pharmacology therefore differs from less selective earlier-generation EGFR inhibitors.
Brain activity
Osimertinib is capable of reaching the central nervous system and has demonstrated activity against EGFR-mutated NSCLC involving the brain in clinical studies.
Why resistance can still occur
Cancer cells can evolve additional molecular changes under treatment pressure. Acquired resistance remains an important clinical issue, and disease progression may require additional molecular testing and treatment reassessment.