CPT 1 inhibition and cancer

Few evidences have been reported in the last 20 years that etomoxir has anti-proliferative properties (ref. 180; 241; 243; 252; 263; 269; 277; 325). Recently, Andreeff, Taegtmeyer and colleaques from the University of Texas broke with the view that in cancer cells glycolysis dominates. They have demonstrated that free fatty acid oxidation largely supports oxygen consumption in leukemia cells and that this process is uncoupled from oxidative phosphorylation.

This constrains leukemia cells to glycolysis for their energy needs in spite of high free fatty acid oxidation. Inhibition of free fatty acid oxidation with etomoxir inhibited proliferation and sensitized human leukemia cells to apoptosis induction by ABT-737. Importantly, etomoxir decreased the number of quiescent leukemia progenitor cells in approximately 50 % of primary human acute myeloid leukemia samples and, when combined with either ABT-737 or cytosine arabinoside, provided substantial therapeutic benefit in a murine model of leukemia. The results support the concept of inhibitors of free fatty acid oxidation as a therapeutic strategy in hematological malignancies (ref. 356).