Polo-like kinase 4 inhibition produces polyploidy and apoptotic death of lung cancers

Significance Despite current treatments, lung cancers remain a major public health problem. Innovative ways are needed to treat or prevent these cancers. Centrosomes are critical for fidelity of mitosis. Abnormal centrosome numbers can cause aberrant mitosis and cell death. Polo-like kinase 4 (PLK4) regulates centriole duplication, and its deregulation alters centrosome number and mitosis. The potent PLK4 inhibitor CFI-400945 is reported here to exert marked antineoplastic effects against lung cancers. CDK2 inhibition also deregulates mitosis and was found to cooperate with PLK4 antagonism. CFI-400945 is now undergoing phase I clinical trial testing (NCT01954316). Taken together, targeting PLK4 for inhibition holds promise in lung cancer therapy either as a single agent or when combined with an agent that deregulates mitosis.