Proteasome inhibition: a novel approach to cancer therapy.

The central role of the proteasome in controlling the expression of regulators of cell proliferation and survival has led to interest in developing proteasome inhibitors as novel anticancer agents. In vitro and in vivo studies have shown that proteasome inhibitors have activity against a variety of tumor types. One of these agents, PS-341, has been tested in phase I trials in a variety of tumor types; in these trials, PS-341 treatment was well tolerated and preliminary evidence of biological activity was observed in some patients. Phase II trials in several hematological malignancies and solid tumor types are now in progress.