Ubiquitin proteasome pathway: implications and advances in cancer therapy

The degradation of most eukaryotic cells is controlled by the ubiquitin proteasome pathway. This pathway is responsible not only for the degradation of short and long-lived proteins but also tumor suppressors, transcription factors and cell cycle proteins. Altered degradation of these proteins is thought to promote cancer growth and spread. By contrast, inhibition of the,proteasome would lead to cell cycle arrest and ultimately programmed cell death, or apoptosis. A structured review of the published literature examining the role of ubiquitin proteasome inhibition in cancer growth and regulation is provided. Advances in the development of proteasome inhibitors have allowed detailed investigation of this pathway in cancer growth. Relevant in vitro and in vivo studies of proteasome inhibition as pertains to cancer therapy are detailed. The ubiquitin proteasome pathway is critical in the degradation of proteins involved in cell cycle control and tumor growth. Proteasome inhibitors have been shown to arrest or retard cancer progression, by interfering with the ordered, temporal degradation of regulatory molecules. Clinical trials examining the agents have begun. (C) 2001 Elsevier Science Ltd. All rights reserved.