Chokα Inhibition: Mechanism of Action and Targeted Therapy

By inhibiting ChoKα, TCD-717 destroys cancer cells with minimal effects on normal cells. Different responses to ChoKα inhibition between cancer and normal cells derives from the addiction of cancer cells to phosphatidylcholine, a phospholipid regulated by ChoKα. While ChoKα inhibition causes a temporary and reversible arrest of proliferation in normal cells, cancer cells attempt to overcome this by activating an alternative mechanism for generating phosphatidylcholine. This enables cancer cells, to some extent, to continue phosphatidylcholine production, but also leads to the production of Ceramide, a lethal metabolite that promotes apoptosis (programmed cell death) causing specific destruction of the cancer cells.

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