Influence of proteasome inhibitors on apoptosis.

PURPOSE OF REVIEW: Proteasome inhibitors are a novel class of drugs that alter normal cellular control of apoptosis. As such, they are being investigated as novel therapies to alter uncontrolled cellular proliferation and treat cancers. This review explores new information about how the proteasome regulates apoptosis and how proteasome inhibitors can be exploited as anti-tumor drugs. RECENT FINDINGS: Proteasome inhibitors block the activation of nuclear factor kappa B in a number of cell systems, as well as altering apoptotic regulatory proteins and intracellular signals that influence the fate of the cell. These effects are true for many tumor cell lines. The US Food and Drug Administration-approved proteasome inhibitor bortezomib blocks erroneous cell proliferation and induces apoptosis in many tumor models. SUMMARY: Proteasome inhibitors have demonstrated promise in vitro, and as a result clinical trials have begun to investigate these agents as therapy for numerous human cancers. Furthermore, newer agents are being designed to inhibit the proteasome system and exert further anti-tumor activity.