Abstract: 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, (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.

Abstract: The present invention involves the identification of sphingoglycolipid species that are indicative of multidrug resistance in certain types of cells, including cancer cells. The association of multidrug resistance with the expression of certain sphingoglycolipids provides a new method for identifying multidrug resistant cancers. In addition, it has been determined that reducing the levels of certain sphingoglycolipids results in enhanced chemosensitivity of drug resistant cancer cells. This offers the opportunity to develop new treatments for multidrug resistant cancers.

Abstract: The present invention provides for the screening of candidate substances to identify active compounds that inhibit multidrug resistance (MDR). The expression of glucosylceramides has been determined to be a marker of MDR. By measuring glucosylceramide expression in cells exhibiting MDR, and the reduction in glucosylceramide levels in the presence of a candidate substance, the present invention provides for the identification of MDR inhibitory compounds.