Polo-like kinase 4 (PLK4) was identified as an anticancer target in an RNA interference (RNAi) screen in human breast cancers and cell lines, and the small molecule CFI-400945 was found to be a potent, selective and orally available PLK4 inhibitor. In vitro studies showed that CFI-400945 treatment recapitulates the hallmarks of genetic PLK4 inhibition, and in vivo studies showed it was well tolerated and had potent antitumour activity in breast cancer xenograft models, particularly those deficient in the tumour suppressor PTEN — a synthetic lethal interaction partner of PLK4. CFI-400945 has entered Phase I clinical trials.
References
Mason, J. M. et al. Functional characterization of CFI-400945, a Polo-like kinase 4 inhibitor, as a potential anticancer agent. Cancer Cell 26, 163–176 (2014)
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Flemming, A. PLK4 inhibitor shows potent antitumour activity. Nat Rev Drug Discov 13, 654 (2014). https://doi.org/10.1038/nrd4430
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DOI: https://doi.org/10.1038/nrd4430
