Targeting proteasome inhibition in hematologic malignancies.
Proteasome inhibitors represent potential novel anti-cancer therapy. These agents inhibit the degradation of multi-ubiquitinated target proteins mediating cell cycle progression, apoptosis, NF-kappa B activation, inflammation, cell cycle regulatory proteins such as cyclins and cyclin dependent kinase inhibitors, as well as immune surveillance; and regulate anti-apoptosis and cell cycle progression. Proteasome inhibitors also directly induce caspase-dependent apoptosis of tumor cells, despite the accumulation of p21 and p27 and irrespective of the p53 wild type or mutant status. Recent studies demonstrate that PS-341, peptide boronate, has remarkable anti-tumor activity in preclinical and clinical studies, not only in multiple myeloma but also in other malignancies.
Hideshima
Teru
T
Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Richardson
Paul G
PG
Anderson
Kenneth C
KC
D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use; D000069286:Bortezomib; D002448:Cell Adhesion / Q000187:drug effects; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D046988:Proteasome Endopeptidase Complex; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use
D001897:Boronic Acids; D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D011719:Pyrazines; D000069286:Bortezomib; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex