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. 2020 Sep 8;9:e58204. doi: 10.7554/eLife.58204

Figure 3. Isobologram analysis showing that SOS1 inhibition synergizes with EGFR-TKI treatment to inhibit survival in multiple EGFR-mutated NSCLC cell lines.

Isobologram analysis and Combination Index (CI) from dose-equivalent treatments of the indicated EGFR-mutated gefitinib-sensitive (L858R or Δex19, top) or gefitinib-resistant (T790M, bottom) NSCLC cell lines with combinations of gefitinib, osimertinib, and BAY-293. Additive effects occur on the dashed lines of the isobologram plot and have a CI 0.8–1.2 (gray box), whereas synergistic interactions fall below the dashed lines and have a CI <0.8. Data are presented as mean +/- s.d. from three independent experiments. For each experiment, three technical replicates were assessed.

Figure 3—source data 1. EGFR mutated NSCLC cell lines are responsive to osimertinib, BAY-293, and gefitinib in 3D spheroid cultures.

Figure 3.

Figure 3—figure supplement 1. EGFR mutated NSCLC cell lines are responsive to osimertinib, BAY-293, and gefitinib in 3D spheroid cultures.

Figure 3—figure supplement 1.

(A-F) Dose-response curves of 3D spheroid cultured HCC827 (A), NCI-H1975 (B), PC9 (C), PC9-TM (D), H3255 (E), or H3255-TM (F) cells to osimertinib (black squares), BAY-293 (red circles) or gefitinib (grey diamonds). Hill coefficients +/- s.d. are shown to the right. Data are presented as mean +/- s.d. from at least three independent experiments. For each experiment, three technical replicates were assessed.