CFI-402257, a TTK inhibitor, effectively suppresses hepatocellular carcinoma

Significance Hepatocellular carcinoma treatments available currently can only prolong the survival of patients for a few months and show a low response rate. Therapeutics that could provide more durable tumor suppression effect are needed. In this study, we characterized CFI-402257, a small molecule inhibitor targeting threonine tyrosine kinase (TTK), as a potential therapeutic drug in hepatocellular carcinoma. CFI-402257 disabled spindle assembly checkpoint, induced cytosolic DNA, activated stimulator of interferon genes (STING) pathway, and stimulated cytokines production in hepatocellular carcinoma cells, which would further promote anti-tumor immunity against hepatocellular carcinoma. Here, we demonstrate CFI-402257 is a potent therapeutic for hepatocellular carcinoma treatment, which targets hepatocellular carcinoma cells directly by inhibiting cell-cycle checkpoint functioning and indirectly by recruiting immune cells from the tumor-microenvironment.

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