TREATMENT OF HYPERPROLIFERATIVE DISORDERS

摘要

A method of treating a hyperproliferative disorder in a subject in need of such treatment, comprising administering to said subject, in combination, a treatment effective amount of: (a) a ceramide-generating retinoid such as fenretinide or a pharmaceutically acceptable salt thereof; and (b) at least one (and in certain embodiments at least two) ceramide degredation inhibitor, such as compounds selected from the group consisting of (i) glucosylceramide synthesis inhibitors and/or 1-acylceramide synthesis inhibitors, (ii) sphingosine-1-phosphate synthesis inhibitors, and (iii) protein kinase C inhibitors. A preferred glucosyl ceramide synthesis inhibitor is 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. A preferred sphingosine-1-phosphate synthesis inhibitor is D-erythro-N,N-dimethylsphingosine. A preferred protein kinase C inhibitor is L-threo-dihydrosphingosine.