Ubiquitin proteasome pathway: implications and advances in cancer therapy

The degradation of most eukaryotic cells is controlled by the ubiquitin pro teasome pathway. This pathway is responsible not only for the degradation o f short and long-lived proteins but also tumor suppressors, transcription f actors arid cell cycle proteins. Altered degradation of these proteins is t hought to promote cancer growth and spread. By contrast, inhibition of the, proteasome would lead to cell cycle arrest and ultimately programmed cell d eath, or apoptosis. A structured review of the published literature examini ng the role of ubiquitin proteasome inhibition in cancer growth and regulat ion is provided. Advances in the development of proteasome inhibitors have allowed detailed investigation of this pathway in cancer growth. Relevant i n vitro and in vivo studies of proteasome inhibition as pertains to cancer therapy are detailed. The ubiquitin proteasome pathway is critical in the d egradation of proteins involved in cell cycle control and tumor growth. Pro teasome inhibitors have been shown to arrest or retard cancer progression, by interfering with the ordered, temporal degradation of regulatory molecul es. Clinical trials examining the agents have begun. (C) 2001 Elsevier Scie nce Ltd. All rights reserved.