Multiple myeloma (MM) is a treatable but incurable disease. Although major progress continues to be made in the treatment of MM with the development of new drugs, such as bortezomib and lenalidomide, drug resistance is still the major hurdle that inevitably results in patient demise. We identified an atypical activation pathway for NF-ƒÛB, a family of gene regulators implicated in drug resistance in MM. Our analysis of primary MM samples indicated that this pathway is critically involved. We propose to determine its role in MM and isolate an inhibitor for it to combat this major clinical problem.