Table 2.
Temporal tumor heterogeneity and acquired TKI resistance in advanced NSCLC
| Mechanisms | Estimated frequency, %
|
References | |
|---|---|---|---|
| Before TKIs | After TKIs | ||
| Resistant EGFR mutations | |||
| T790M | 1–2 | 50 | 57,97,109,139 |
| D761Y, L747S, and T854A | <1 | <5 | 12,76 |
| Bypass signaling | |||
| MET amplification | <5 | 5–20 | 12,130,139 |
| HGF overexpression | 30 | 60 | 140,141 |
| HER2 amplification | 2 | 12 | 142 |
| PIK3CA mutations | 2–3 | 5 | 112,143 |
| CRKL amplification | 3 | 9 | 144,145 |
| Phenotypic changes | |||
| Small-cell transformation | <1 | 3–14 | 57,112 |
| EMT | <1 | 20–44 | 26,133 |
Abbreviations: TKI, tyrosine kinase inhibitor; NSCLC, nonsmall cell lung cancer; EGFR, epidermal growth factor receptor; HGF, hepatocyte growth factor; HER2, human epidermal growth factor receptor 2; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; CRKL, CRK-like protein gene; EMT, epithelial-mesenchymal transition.