Indeed, fenretinide [N-(4-hydroxyphenil)retinamide; 4-HPR], a synthetic derivative of all-trans retinoic acid characterized by high cytotoxic efficacy against cancer cells in vitro, was the first chemotherapeutic drug found to inhibit DES1, resulting in a reduction of the Cer de novo biosynthesis and the accumulation of endogenous dhCers [96]. This evidence concerns the gene CBLN1 and cancer.