Use of bortezomib in B-cell non-Hodgkin's lymphoma.

The ubiquitin-proteasome pathway plays a critical role in the regulated degradation of proteins involved in cell cycle control and tumor growth. Bortezomib (Velcade, formerly known as PS-341) is a potent proteasome inhibitor. In preclinical studies, bortezomib has demonstrated activity against a variety of B-cell malignancies by inducing apoptosis and sensitizing tumor cells to radiation or chemotherapy. Based on these findings, clinical trials have been conducted with bortezomib in B-cell non-Hodgkin's lymphoma. In these studies, bortezomib was generally well tolerated with manageable toxicities and showed promising clinical activity. Mantle cell lymphoma was significantly more sensitive to bortezomib than other non-Hodgkin's lymphomas. Bortezomib may have far-reaching potential in the treatment of B-cell non-Hodgkin's lymphoma.