Table 2.
Summary of reported bypass tracks conferring resistance to ALK TKIs.
| Protein Alteration (Upregulation Unless Otherwise Specified) |
ALK TKI | Disease |
|---|---|---|
| IGF-1R | Crizotinib [129,130] | NSCLC and ALCL |
| Epidermal growth factor receptor (EGFR) | Crizotinib [78,81,98,131,132] Ceritinib [98,133] Alectinib [98,132,134] Lorlatinib [124,132] |
NSCLC |
| Lorlatinib [124] | Neuroblastoma | |
| Human epidermal growth factor receptor (HER), including via increased neuregulin 1 ligand | Ceritinib and alectinib [135,136] | NSCLC |
| KIT proto-oncogene receptor tyrosine kinase (KIT), including via increased stem cell factor (SCF) ligand | Crizotinib [78] Ceritinib [98] |
NSCLC |
| MET proto-oncogene receptor tyrosine kinase (MET), including via increased hepatocyte growth factor (HGF) ligand | Alectinib [134,137,138,139,140] Ceritinib and lorlatinib [79,98,117] |
NSCLC |
| SRC proto-oncogene, non-receptor tyrosine kinase (SRC) | Crizotinib [141] Alectinib [138] |
NSCLC |
| Discoidin domain receptor tyrosine kinase 2 (DDR2) | Alectinib [79] | NSCLC |
| Fibroblast growth factor receptor 2 (FGFR2) | Ceritinib [79] | NSCLC |
| ERb-B4 receptor tyrosine kinase 4 (ErbB4) | Lorlatinib [124] | Neuroblastoma |
| Interleukin 10 receptor subunit alpha (IL10RA) | Crizotinib [142] Alectinib [142] Brigatinib [142] Lorlatinib [142] |
ALCL |
| Protein tyrosine phosphatase non-receptor tyrosine kinase 1/2 (PTPN1/2) loss | Crizotinib [143] | ALCL |