Proteasome Inhibition: a New Strategy in Cancer Treatment

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Abstract
The ubiquitin proteasome pathway is a highly conservedintracellular pathway for the degradation of proteins. Many of theshort-lived regulatory proteins which govern cell division, growth,activation, signaling and transcription are substrates that aretemporally degraded by the proteasome. In recent years, new andselective inhibitors of the proteasome have been employed in cellculture systems to examine the anti-tumor potential of theseagents. This review covers the chemistry of selected proteasomeinhibitors, possible mechanisms of action in cell culture and thein vivo examination of proteasome inhibitors in murine andhuman xenograft tumor models in mice. One inhibitor, PS-341, hasrecently entered Phase I clinical trials in cancer patients withadvanced disease to further test the potential of this approach.