Proteasome inhibition: a new therapeutic strategy to cancer treatment.
The ubiquitin-proteasome system is a major pathway for protein degradation. Targeting this pathway using proteasome inhibitors represents a novel approach for the treatment of cancer. Proteasome inhibitors lower cell proliferation and induce apoptosis in solid and hematologic malignancies through multiple mechanisms, including stabilization of cell cycle regulators and pro-apoptotic factors, stimulation of bone morphogenetic protein signaling, inhibition of protein translation, and sensitization to ligand-induced apoptosis. In this connection, proteasome inhibition activates macroautophagy, a compensatory protein degradation system, as well as other pro-survival signaling pathways. Inhibition of these auto-protective responses sensitizes cancer cells to the anti-proliferative effects of proteasome inhibitors.
Institute of Digestive Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
William Ka Kei
WK
Wu
Chi Hin
CH
Cho
Chung Wa
CW
Lee
Kaichun
K
Wu
Daiming
D
Fan
Jun
J
Yu
Joseph Jao Yiu
JJ
Sung
D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors
D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex