[A new therapy with bortezomib, an oncologic medicinal product of the year 2004].
Proteasome-mediated proteolysis is a mechanism for mediating important regulatory proteins within the cell. Proteins that have been targeted for degradation by the proteasome are convalently tagged with a poly-ubiquitin protein chain prior to be recognized by the 19S subunit of proteasome. This degradation system controls the expression of a wide variety of cellular targets including tumor suppressors such as p53, inhibitor of nuclear factor NFkappaB, cyclin-dependent kinase inhibitors such as p21 and p27. Because of these functions, the proteasome has become a new target for cancer treatment. The potent and selective proteasome inhibitor, PS-341 or Velcade was approved in the United States and launched in may 2003 for the treatment of multiple myeloma patients who have received at least two prior therapies. On April 2004, the European commission granted marketing authorization for Velcade with the same indication. The same year 2004, the Nobel Prize in chemistry was awarded to three researchers "for the discovery of ubitiquin-mediated protein degradation", a regulated process by which proteins are cleaved into peptides inside cells.
Monneret
Cl
C
Département de pharmacochimie, Institut Curie, Paris. Claude.Monneret@curie.fr
Buisson
J P
JP
Magdelenat
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D046988:Proteasome Endopeptidase Complex; D011719:Pyrazines / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex