Similarly, inhibition of NOTCH2, the expression of which has been shown to be related to well-differentiated iCCA155, markedly reduced tumour burden in various mouse models of liver cancer (including iCCA)81,159, whereas overexpression of NOTCH3 was associated with the development and progression of iCCA, promoting cell survival via PI3K–AKT signalling160. This evidence concerns the gene AKT1 and infantile convulsions and choreoathetosis.