Multiple Myeloma is an incurable blood cancer representing approximately 2% of all cancer deaths. Recently, FDA approved Bortezomib for the treatment of patients with relapsed myeloma. Bortezomib has several putative targets including the transcription factor NF-kB. We have found that blocking NF-kB activation increased sensitivity of myeloma cells to Bortezomib cytotoxicity. In this project, we propose to validate this finding using a myeloma mouse model. Our work will provide an important pre-clinical in vivo evidence for the development of a new therapeutic modality involving a combined regimen of BMS-345541, an NF-kB inhibitor, and Bortezomib in multiple myeloma therapy.