Bortezomib as an antitumor agent.
The ubiquitin-proteasome pathway (UPP) is the major non-lysosomal proteolytic system in the cytosol and nucleus of all eukaryotic cells. Bortezomib (also known as PS-341 and Velcade) is a proteasome inhibitor, a novel class of cancer therapies. Bortezomib blocks multi-ubiquitinated protein degradation by inhibiting 26S proteasome activity, including regulating cell cycle, anti-apoptosis, and inflammation, as well as immune surveillance. In multiple myeloma (MM) cells, bortezomib directly induces cell stress response followed by activation of c-Jun NH(2) terminal kinase (JNK)/stress-activated protein kinase (SAPK), and triggers caspase-dependent apoptosis of tumor cells. Recent clinical studies demonstrated that bortezomib had remarkable anti-tumor activity in refractory and relapsed MM, providing the basis to approval by FDA. Its anti-tumor activities earlier in the course, in combination therapies, and in other malignancies is ongoing.
Roccaro
A M
AM
Department of 1Internal Medicine and Oncology, University of Bari MedicalSchool, Bari, Italy.
Hideshima
T
T
Richardson
P G
PG
Russo
D
D
Ribatti
D
D
Vacca
A
A
Dammacco
F
F
Anderson
K C
KC
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011719:Pyrazines / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects*; D025801:Ubiquitin / Q000378:metabolism*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D025801:Ubiquitin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex