Conversely, its expression in adult human tissues is limited to the central nervous system, to vascular smooth muscle cells41 and to very few subset of B cells.42 Thus, Notch3 aberrant expression in human cancers represents a promising target for therapeutic treatment.11,16,43,44 Herein, we have shown that Notch3 regulates Aco1, Mdh1 and Idh1, three important enzymes of the TCA cycle leading to brivanib resistance in HCC. The gene discussed is ACO1; the disease is hepatocellular carcinoma.