Table 1.
IC50 (μM) values from cell growth inhibition assays comparing compound sensitivity between parental and resistant cell populations.
Cells were treated with dose titrations of indicated inhibitors alone for parental cells and in the presence of original EGFR inhibitor for resistant populations. IC50 values represent an average of at least 2 independent experiments. Errors are standard deviation. Additional compound data is shown in Supplementary Table S3.
| Cell population | Genetic alterations detected within resistant populations | (MEK1/2) | (EGFR) |
|---|---|---|---|
| PC9 | 6.95 (±2.5) | 0.008 (±0.002) | |
| PC9 GR_1 | EGFR T790M / KRAS gain (5.43 fold) | 7.24 (±3.2) | 1.12 (±0.5) |
| PC9 GR_2 | NRAS E63K | 0.62 (±0.3) | 2.8 (±0.4) |
| PC9 GR_3 | EGFR T790M | 6.2 (±3.6) | 0.18 (±0.2) |
| PC9 GR_4 | EGFR T790M | 7.32 (±2.3) | 0.02 (±0.01) |
| PC9 GR_5 | EGFR T790M | 8.77 (±1.5) | 0.14 (±0.06) |
| PC9 GR_6 | EGFR T790M | 7.44 (±2.6) | 0.005 (±0.001) |
| PC9 GR_7 | EGFR T790M | 3.7 (±0.99) | 0.002 (±0.002) |
| PC9 GR_8 | EGFR T790M / KRAS gain (7.06 fold) | 2.48 (±1.4) | 2.40 (±0.97) |
| PC9 AR_1 | KRAS gain (24.6 fold) | 2.7 (±0.23) | 2.41 (±0.5) |
| PC9 AR_4 | EGFR T790M | 1.63 (±1.1) | 0.73 (±0.3) |
| PC9 AR_6 | NRAS gain (4.23 fold) | 0.89 (±0.6) | 2.4 (±0.5) |
| PC9 WZR_1 | NRAS Q61K | 0.23 (±0.04) | 1.99 (±0.03) |
| PC9 WZR_3 | KRAS gain (2.64 fold) | 0.22 (±0.1) | 1.65 (±0.5) |
| PC9 AZDR_1 | NRAS gain (2.5 fold) / MAPK1 gain / CRKL gain | 0.25 (±0.06) | 2.3 (±0.9) |
| PC9 AZDR_2 | NRAS G12V | 1.4 (±0.9) | 3.69 (±1.2) |
| PC9 AZDR_3 | MAPK1 gain / CRKL gain | 2.38 (±0.9) | 1.94 (±0.5) |
| PC9 AZDR_4 | ND | 0.19 (±0.1) | 2.48 (±1.1) |
| PC9 AZDR_5 | NRAS E63K | 0.17 (±0.05) | 2.14 (±0.06) |
| PC9 AZDR_6 | NRAS E63K | 0.11 (±0.03) | 1.6 (±0.02) |
| PC9 AZDR_7 | NRAS G12R | 0.14 (±0.03) | 2.63 (±0.3) |
| PC9 GR_1_AZDR_1 | EGFR T790M / KRAS gain (6.23 fold) | 3.6 (±0.7) | 2.4 (±0.95) |
| PC9 GR_1_AZDR_2 | KRAS gain (5.66 fold) | 6.7 (±1.4) | 2.7 (±1.2) |
| PC9 GR_1_AZDR_3 | EGFR T790M / KRAS gain (4.44 fold) | 3.4 (±0.5) | 2.4 (±0.7) |
| PC9 GR_1_AZDR_4 | EGFR T790M / KRAS gain (5.46 fold) | 3.6 (±2.6) | 2.6 (±0.9) |
| PC9 GR_6_AZDR_1 | ND | 0.28 (±0.2) | 1.35 (±0.05) |
| PC9 GR_6_AZDR_2 | NRAS gain (2.4 fold) | 0.54 (±0.3) | 2.24 (±0.6) |
| PC9 GR_6_AZDR_3 | NRAS gain (3.68 fold) | 0.13 (±0.06) | 1.48 (±0.3) |
| PC9 GR_6_AZDR_4 | ND | 0.73 (±0.5) | 1.74 (±0.8) |
| NCI-H1975 | EGFR T790M | 4.94 (±3) | 0.016 (±0.01) |
| NCI-H1975 AZDR_1 | EGFR T790M | 0.024 (±0.003) | 2.52 (±0.4) |
| NCI-H1975 AZDR_2 | EGFR T790M | 0.15 (±0.1) | 2.21 (±0.2) |
| NCI-H1975 AZDR_3 | EGFR T790M | >10 | 3.04 (±0.4) |
| NCI-H1975 AZDR_4 | EGFR T790M / NRAS Q61K | 5.46 (±3.7) | 2.67 (±0.7) |
DNA from resistant populations was analysed for gene mutation and/or gene copy number across a panel of cancer associated genes. Data represents genetic alterations detected within the resistant populations. Fold gain, relative to parental cells, indicated in brackets for NRAS and KRAS. Non detected (ND)