| Autor: |
Goranov SE; Clinic of Hematology, University hospital 'St George', Plovdiv, 15A Vassil Aprilov St., 4002 Plovdiv, Bulgaria., Goranova-Marinova VS |
| Jazyk: |
angličtina |
| Zdroj: |
Folia medica [Folia Med (Plovdiv)] 2005; Vol. 47 (3-4), pp. 11-9. |
| Abstrakt: |
Proteasome inhibitors are emerging as a promising class of anti-cancer therapeutic agents. The first of this new class of drugs with a clinical significance, bortezomib (PS 341, Velcade), is a modified dipeptidyl boronic acid. Bortezomib reduces the NF-kappaB translocation / transcription and blocks the drug-related signalling pathways critical to basic vital functions of myeloma cells. Bortezomib induces apoptosis by releasing cytochrome C from mitochondria and by activating caspase-9 and Jun-kinases (JNK) and the Fas-caspase-8-dependent apoptotic pathway. Bortezomib has been reported to down-regulate cytokine-induced expression of VCAM-1, a major ligand on bone marrow stromal cells for VLA-4; it inhibits the heterotypic adherence between the myeloma cells and stromal cells and blocks the signalling pathways of resistance to apoptosis. The drug has been shown experimentally to inhibit the IL-6-induced proliferation of myeloma cells; it demonstrates synergy with dexamethasone and inhibits angiogenesis. Phase II/ III clinical studies with Velcade have shown an overall therapeutic response rate of 35% in refractory, relapsed myeloma patients (Bladé criteria). These surprisingly good results, the drug's good tolerance and controllable side effects provide a solid base for further studies on bortezomib, including studies on the drug used as front line therapy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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