BACKGROUND: The ubiquitin-proteasome system has become a promising novel 
molecular target in cancer due to its critical role in cellular protein 
degradation, its interaction with cell cycle and apoptosis regulation and its 
unique mechanism of action.
OBJECTIVE: This review focuses both on preclinical results and on data from 
clinical trials with proteasome inhibitors in cancer.
METHODS: Results in hematological malignancies and solid tumors were included, 
and important data presented in abstract form were considered in this review.
RESULTS/CONCLUSION: Bortezomib as first-in-class proteasome inhibitor has proven 
to be highly effective in some hematological malignancies, overcomes 
conventional chemoresistance, directly induces cell cycle arrest and apoptosis, 
and also targets the tumor microenvironment. It has been granted approval by the 
FDA for relapsed multiple myeloma, and recently for relapsed mantle cell 
lymphoma. Combination chemotherapy regimens have been developed providing high 
remission rates and remission quality in frontline treatment or in the relapsed 
setting in multiple myeloma. The combination of proteasome inhibition with novel 
targeted therapies is an emerging field in oncology. Moreover, novel proteasome 
inhibitors, such as NPI-0052 and carfilzomib, have been developed. This review 
summarizes our knowledge of the ubiquitin-proteasome system and recent data from 
cancer clinical trials.