Skip to main content

Table 4 Main mechanisms involved in acquired resistance to EGF receptor-tyrosine kinase inhibitors and the associated targetable drugs

From: Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer

Molecular alteration Pathway Targetable drug
HER2 amplification   Afatinib, Trastuzumab, ado-trastuzumab emtansine (TDM1)
MET overexpression/genetic alteration    Anti-HGF antibody: Rilotumumab, Ficlatuzumab
 Anti-c-MET antibody: MET Mab, Emibetuzumab (LY2875358)
 Selective c-MET inhibitor: Tivantinib (ARQ197), Capmatinib (INC280),
            Savolitinib (AZD6094), Tepotinib (EMD 1214063),
            SGX523, SAR125844,
 Multikinase inhibitors: Crizotinib, Cabozantinib (XL184), Glesatinib (MGCD265),
           Merestinib (LY2801653), S49076
PIK3CA PI3K-AKT-mTOR  PI3K inhibitor: Pilaralisib (XL147), Dactolisib (BEZ235) and Pictilisib (GDC-0941),
        Buparlisib (BKM120)
 AKT inhibitor: MK-2206
 mTOR inhibitor: Everolimus, Temsirolimus, Ridaforolimus
BRAF Ras-Raf-MEK-ERK Vemurafenib (PLX4032), Dabrafenib (GSK2118436), Selumetinib, LY3009120
AXL overexpression GAS6-AXL  Tyrosine kinase inhibitor: Cabozantinib (XL 184)
 AXL antibody: E8, D9, Mab173
 AXL decoy receptor: AXL-Fc, MYDI