Figure 1. Efficacy of combination treatments in non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) cell lines.

a, Comparison of combination scores (cScore) indicating the response of the KRAS^G12C mutant NSCLC cell line, NCI-H2122, to the combination treatment of AMG 510 or adagrasib with 179 other small molecules for 72 hours. Positive scores indicate synergistic effects with scores >5–10 generally considered “clear synergy.” Empty or yellow/blue coloured circles highlight selected compounds for reference. b, Comparison of combination scores (cScore) indicating the response of KRAS^G12C mutant CRC cell line, SW837, to the combination treatment of AMG 510 or adagrasib with 15 other small molecules for 96 hours. Positive scores indicate synergistic effects with scores >5–10 generally considered “clear synergy”. Empty or yellow/blue coloured circles highlight selected compounds for reference. c, Response of indicated cell line to the combination treatment of adagrasib with an SOS1 inhibitor (BI-3406), a SHP2 inhibitor (TNO155 or SHP099), or an EGFR inhibitor (cetuximab). Cell lines are indicated as colorectal cancer (CRC; orange), esophageal (light blue), or non-small cell lung cancer (NSCLC; dark blue). MAPK Pathway Activity Score (MPAS) are indicated. d, Growth kinetic of NCI-H2122 (right) or SW837 (left) cells treated with indicated single or combination treatments, or vehicle control (N=3 for each curve). Y-axis indicates change in confluency relative to t=0 hours. Inset shows boxed area for clarity. Mean ± SEM shown. Data analyzed by one-way analysis of variance (ANOVA) with Tukey’s multiple comparisons test.