Proteosome Inhibitors

Bortezomib is a dipeptidyl boronic acid proteosome inhibitor that effectively and specifically inhibits pro-teosome activity. The proteosome controls the stability of numerous proteins that regulate progression through the cell cycle and apoptosis, such as cyclins, cyclin-dependent kinases, tumor suppressors, and the nuclear factor-KB.72 By altering the stability or activity of these proteins, proteosome inhibitors sensitize malignant cells to apoptosis. In preclinical studies, bortezomib and other proteosome inhibitors have shown activity against a variety of B-cell malignancies, including multiple myeloma, diffuse large B-cell lymphoma, mantle cell lymphoma, and Hodgkin's lym-phoma.73 74 Based on these findings, phase I clinical trials were conducted with bortezomib in various solid and hematologic malignancies. Phase II trials have been initiated for refractory chronic lymphocytic leukemia and non-Hodgkin's lymphoma.75

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