Network-based targeting strategies represent a promising therapeutic approach for the treatment of diseases that lack strong and actionable drivers. Using an integrated phenotypic screening and phosphoproteomics strategy, Kuenzi et al. report that the FDA-approved ALK inhibitor ceritinib exhibits activity in several ALK-negative non-small-cell lung cancer cell lines through simultaneous inhibition of multiple non-canonical targets (namely FAK1, IGF1R, RSK1 and RSK2), which is largely dependent on the downstream signalling effector YB1. Ceritinib synergized with paclitaxel, particularly in cells expressing high FAK1 autophosphorylation.
References
Kuenzi, B. et al. Polypharmacology-based ceritinib repurposing using integrated functional proteomics. Nat.Chem. Biol. http://dx.doi.org/10.1038/nchembio.2489 (2017)
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Crunkhorn, S. Repurposing ceritinib. Nat Rev Drug Discov 16, 828 (2017). https://doi.org/10.1038/nrd.2017.233
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DOI: https://doi.org/10.1038/nrd.2017.233