The use of targeted agents, such as Velcade, represents a major advance over the use of standard chemotherapy but is not universally effective. Combinations of targeted agents have the potential to attack different pathways responsible for cancer cell survival, and represent a new approach as most cancers are dependent upon several pathways. Our lab has generated data indicating that the combination of farnesyl transferase inhibitors with Velcade results in more myeloma cell death than when either agent is used alone. We propose to test why this occurs and to initiate a phase I trial combining these agents.