[Proteasome inhibition: a new therapeutic approach for the treatment of multiple myeloma].
Multiple myeloma is the second most common hematologic malignancy with currently no definitive treatment available. Although, therapy may include allogenic bone marrow transplantation, high-dose ablative chemotherapy followed by bone marrow or peripheral stem cell transplantation, melphalan/corticosteroid therapy, alpha-interferon treatment, and combined cytostatic chemotherapy, currently none of these alternatives offer cure for the disease. Introduction of thalidomide into the therapeutic arsenal provided a breakthrough in the treatment of refractory and/or relapsing disease, however, clinical experience indicated need for alternative treatments for thalidomide resistant disease as well as for intolerant patients. Proteasome inhibitors, hallmarked by bortezomib may represent one of the much needed therapeutic options. The results of the SUMMIT investigation that involved 202 heavily pretreated patients were convincing enough to prompt the FDA to register this drug for the treatment of multiple myeloma. Its European registration is also underway. In this review, the proteasome and its inhibition as a pharmacotherapeutic avenue are introduced. The most important clinical studies employing bortezomib and its combinations are also detailed. It is the hope of the authors that bortezomib and its derivatives will soon belong to the clinical armory against multiple myeloma.
Mikala
Gábor
G
Országos Gyógyintézeti Központ, Hematológiai és Hemosztaziológiai Osztály, Budapest.
Jákó
János
J
Vályi-Nagy
István
I
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D017321:Clinical Trials, Phase I as Topic; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000201:enzymology*; D046988:Proteasome Endopeptidase Complex; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents; D001897:Boronic Acids; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D011719:Pyrazines; D000069286:Bortezomib; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex