The proteasome, a new target for cancer therapy.
The proteasome is a multicatalytic protease and the principal non-lysosomal proteolytic system in all eukaryotic cells. It plays a central role in virtually all regulatory pathways as for instance cell-cycle regulation, differentiation, and apoptosis. The proteasome degrades regulatory proteins and their inhibitors and, thus is an interesting target for therapeutic drugs. Inhibitors of the proteasome are small molecules that function by stabilizing various proteins, including cell-cycle regulators, tumor suppressors and growth factors. Because proteasome inhibition blocks cellular proliferation and induces apoptosis, these agents have been tested as anticancer drugs in tumor models and have shown impressive potential. In addition, treatment with proteasome inhibitors can sensitize cells to other cancer treatments like radio- or chemotherapy. This review introduces the ubiquitin-proteasome pathway and outlines the recent progress in the development of proteasome inhibition as a treatment option for clinical cancer therapy.
Gillessen
S
S
Department of Oncology/Hematology, Kantonsspital St. Gallen, Switzerland. silke.gillessen@kssg.ch
Groettup
M
M
Cerny
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002986:Clinical Trials as Topic; D003546:Cysteine Endopeptidases / Q000502:physiology; D004341:Drug Evaluation; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex