Selective degradation of proteins by the ubiquitin-proteasome pathway is a 
critical determinant for maintaining cellular homeostasis. Most intracellular 
proteins are degraded by the proteasome, a multicatalytic enzyme complex 
containing a 20S catalytic core and two 19S regulatory complexes. Many 
proteasome target proteins are involved in the regulation of important processes 
of carcinogenesis and cancer cell survival, such as cell cycle progression, cell 
proliferation, differentiation and apoptosis. Indeed, the 
ubiquitin-proteasome-dependent degradation pathway plays an essential role in 
both the up-regulation of cell proliferation and down-regulation of cell death 
in human cancer cells. Both in vitro and in vivo experimental and clinical 
results have demonstrated the potential use of proteasome inhibitors as novel 
anticancer drugs. Proteasome inhibition in cancer cells leads to accumulation of 
pro-apoptotic target proteins followed by induction of cell death. The clinical 
efficacy of the proteasome inhibitor bortezomib toward multiple myeloma and 
other hematologic malignancies provides the "proof of concept" that targeting 
the proteasome is a promising strategy for cancer treatment. Several other 
proteasome inhibitors have also been identified from natural resources, such as 
marine microbial metabolites, green tea polyphenols, flavonoids, and medicinal 
compounds. Additionally, the use of metal complexes as proteasome inhibitors has 
also been investigated as a potential anticancer strategy. The clinical 
significance of targeting the tumor survival-associated proteasome pathway for 
cancer treatment, intervention and prevention will be discussed.