EGFR

About EGFR

EGFR Epidermal Growth Factor Receptor on chromosome 7p11.2 encodes a receptor tyrosine kinase of the ErbB family that activates the RAS MAPK and PI3K AKT pathways when bound by ligands such as epidermal growth factor. Stanley Cohen shared the 1986 Nobel Prize for the discovery of epidermal growth factor. Activating EGFR mutations, especially exon 19 deletions and the L858R point mutation in the kinase domain, occur in a minority of lung adenocarcinomas in Western populations and are considerably more common in East Asian patients and in people who have never smoked. These mutations predict strong responses to EGFR tyrosine kinase inhibitors, a discovery reported in 2004. First generation erlotinib and gefitinib, the second generation afatinib, and the third generation osimertinib transformed treatment of EGFR mutant non small cell lung cancer, with osimertinib also showing good activity against brain metastases. Resistance develops through the T790M mutation for earlier inhibitors, C797S for osimertinib, and bypass pathways such as MET amplification. EGFR amplification and the EGFRvIII variant are common in glioblastoma. The antibodies cetuximab and panitumumab target EGFR in RAS wild type colorectal cancer.