Bortezomib-combination based therapy in relapsed-refractory myeloma patients

The encouraging results obtained by Bortezomib (Velcade®) as single agent in relapsed-resistant multiple myeloma (MM) patients has brought to test effective combinations with conventional myeloma agents in order to improve the response and the survival of this difficult setting of patients. The main action of Bortezomib (Velcade®) is the inhibition of the transcription factor NF-kB, down regulating the expression of several apoptosis inhibitors, and inducing apoptosis of drug resistant multiple myeloma cell lines. Moreover, the inhibition of NF-kB determines a down regulated transcription of several effectors of the protective cellular response to genotoxic stress, like topoisomerase II beta. As a consequence, Bortezomib (Velcade®) sensitizes myeloma cells to chemotherapy and overcomes resistance to genotoxic agents.