Table 1.
Characteristics (left) and IC50s (µM, right) for selected drugs of the PC9-derived cell lines used in the study
| Cell line | Doublintg time (h) | EGFR Del19 | EGFR 790 M | AXL overexpression | MET activation | FGFR1 overexpression | Gefitinib (EGFR) | Erlotinib (EGFR) | Afatinib (EGFR) | Osimertinib (EGFR) | S49076 (AXL, MET, FGFR1, AURKB) | Foretinib (MET, KDR, AXL, AURKB) | Crizotinib (MET, ALK) | Capmatinib (MET) | BGB324 (AXL) | Nintedanib (FGFR) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PC9 | 24 ± 2 | + | v− | − | − | − | 0.04 | 0.005 | 0.003 | 0.05 | >50 | 1.6 | 2.0 | >25 | 2.3 | 11.4 |
| PC9-GR1 | 27 ± 3 | + | + | − | + | − | 12.2 | 4.8 | 0.4 | 0.03 | >50 | 1.5 | 2.4 | >25 | 2.3 | 14.3 |
| PC9-GR2 | 31 ± 1 | + | − | + | + | − | 14.9 | 25.0 | 3.8 | 3.0 | 1.2 | 0.6 | 2.3 | >25 | 2.5 | 5.7 |
| PC9-GR3 | 30 ± 1 | + | − | + | − | − | 15.8 | 33.7 | 4.8 | 5.5 | 0.3 | 0.5 | 1.0 | >25 | 2.7 | 8.1 |
| PC9-GR4 | 29 ± 1 | + | + | + | − | − | 6.5 | 3.8 | 0.4 | 0.02 | >50 | 3.6 | 2.1 | >25 | 3.3 | 12.5 |
| PC9-GR5 | 31 ± 5 | + | − | ++ | − | ++ | 18.1 | 21.8 | 3.6 | 5.3 | 0.9 | 0.6 | 2.1 | 19.8 | 2.7 | 2.3 |
| PC9-ER | 27 ± 2 | + | − | ++ | − | − | 12.2 | 28.6 | 6.8 | 3.2 | 0.3 | 0.7 | 1.4 | >25 | 3.3 | 7.8 |
| PC9-GR1-AZD1 | 32 ± 5 | − | − | ++ | − | − | 21.0 | 43.9 | 15.3 | 8.3 | 0.2 | 0.6 | 0.7 | >25 | 2.1 | 24.2 |
| PC9-GR1-AZD2 | 25 ± 4 | − | − | ++ | − | − | 20.0 | 49.8 | 17.0 | 8.8 | 0.3 | 0.7 | 1.3 | >25 | 2.4 | 13.3 |
| PC9-GR1-AZD3 | 26 ± 6 | + | − | + | + | − | 18.7 | 42.4 | 15.4 | 5.7 | 0.2 | 0.6 | 0.6 | >25 | 2.1 | 24.9 |
| PC9-GR1-AZD4 | 30 ± 3 | − | − | + | − | − | 18.2 | 35.5 | 13.5 | 6.4 | 0.3 | 0.7 | 0.7 | >25 | 2.1 | 14.3 |
| PC9-GR4-AZD1 | 26 ± 4 | + | + | + | − | − | 10.5 | 43.2 | 7.1 | 5.1 | >50 | 2.5 | 1.9 | 21.9 | 2.6 | 13.7 |
| PC9-GR4-AZD2 | 34 ± 7 | + | +a | − | − | + | 13.7 | 41.2 | 2.6 | 7.5 | 0.4 | 4.2 | 5.8 | >25 | 2.3 | 22.2 |
| H1975 | 21 ± 1 | − | + | − | nd | − | 9.1 | 24.5 | 0.0005 | 0.23 | 22.1 | 2.5 | 1.5 | nd | 1.8 | nd |
The H1975 cell line is also included in the table. The targets of the drugs are indicated between parentheses. Doubling times are expressed as means ± SD of at least three different determinations
aAllelic fraction 0.03%