Table 4.
Resistance mechanisms in EML4‐ALK+positive NSCLC patients.
| Types of resistance mechanisms | ||
|---|---|---|
| On‐target resistance | Off‐target resistance | Additional resistance |
| ATP site Gatekeeper mutations [64] | KRAS‐exon 3 mutation [52] | Anti‐apoptotic pathways [93] |
|
ATP site solvent‐front mutations (e.g.: G1202R) [64] |
MET amplification [64] | Histological transformation [94] |
| Second‐site mutations [46, 95] | MEK activation [96] | Epigenetics [97] |
| Compound mutations | PIK3CA mutations [98] | Tumour microenvironment [29] |
| Oncogene amplification [46] | IGF‐1R activation [56] | |
| Oncogene loss [46] | KRAS G12C mutation [46] | |
| ALK‐exon 23 mutation [52] | RET fusion [52] | |
| MAPK pathway [68] | ||
| TP53 mutation [44] | ||
| PI3K‐AKT pathway [99] | ||
| JAK–STAT pathway [60] | ||
| SRC activation [100] | ||
| EGFR activation [58] | ||
| KIT activation [64] | ||
|
HER family activation [58] |
||