Desmethyl-clomipramine (DCMI), the active metabolite of clomipramine, inhibits both ITCH autoubiquitylation and its ubiquitylation of p73, enhancing the cytotoxic effects of standard chemotherapeutics in various cancers (297, 298) In glioblastoma, gain-of-function TP53 mutations in astrocytes upregulate ITCH, leading to ferritin heavy chain (FTH) degradation and increased free iron levels (299). This evidence concerns the gene ITCH and cancer.