ABSTRACT
The proteasome is responsible for degradation of many intracellular proteins, thereby helping maintain the cellular homeostasis during biological processes such as cell cycle, signal transduction, response to stress and gene transcription. In multiple myeloma, proteasome inhibitors have been shown to be very successful. The therapeutic index for proteasome inhibitors is favorable. More than 80% of all eukaryotic protein degradation is controlled by the ubiquitin-proteasome pathway. Proteasome inhibitors block cancer progression by interfering with the degradation of regulatory proteins. The most frequently described and well-known proteasome inhibitor is bortezomib, a dipeptide boronic acid analog with a broad antitumor activity in several cell lines and murine and human tumor models. Already in 1990, it was shown that human leukemic cells expressed abnormally high levels of proteasomes compared with normal peripheral blood cells. Many of the initial studies regarding the effect of proteasome inhibition have been performed in in vitro systems.
