Fig. 1: Synergistic dual combinations for mutant KRAS lung cancer obtained through a drug repurposing-based strategy. | Nature Communications

Fig. 1: Synergistic dual combinations for mutant KRAS lung cancer obtained through a drug repurposing-based strategy.

From: Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer

Fig. 1: Synergistic dual combinations for mutant KRAS lung cancer obtained through a drug repurposing-based strategy.The alternative text for this image may have been generated using AI.

A Experimental workflow employed to identify drug combinations with the highest antitumor effect on mutant (mut) KRAS LUAD. B Repurposing scores of drugs obtained from the Connectivity Map at the Library of Integrated Network-based Cellular Signatures (LINCS) program (c3.lincscloud.org) using the interspecies KRAS signature as input. Targets of predicted drugs are shown in brackets. C Combination index (CI) values corresponding to all concentrations for each drug-pair combination tested in mut KRAS cell lines (H1792 and H2009; n = 9). CI < 0.8, synergism. Trametinib (Tram: MEK1/2i); BIX02189 (BIX: MEK5-Kinase2i); Neratinib (Nera: ERRB2i, EGFRi); Lestaurtinib (Lest: PKCi), Dabrafenib (Dabra: BRAFi, CRAFi); Adavosertib (Adavo: WEE1i), Panobinostat (Pano: HDACi). Data: mean +/− SEM. D, E Percent cell viability of H1792 and H2009 cells treated with different concentrations of Tram and Lest (D) or Tram and Adavo (E), individually or in combination (data from the drug screening). F Principal component analysis (PCA) of H1792 cells treated with DMSO (Ctrl), Tram or Lest. G Unsupervised clustering heatmap of iKRASsig genes’ expression in H1792 cells treated with DMSO (Ctrl), Tram or Lest.

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