Title:The Immunoproteasome as a Therapeutic Target for Hematological Malignancies
Volume: 14
Issue: 6
Author(s): Zachary Miller, Wooin Lee and Kyung Bo Kim
Affiliation:
Keywords:
Constitutive proteasome, immunoproteasome, mantle cell lymphoma, multiple myeloma, small molecule inhibitors,
subunit-selective inhibitor.
Abstract: Remarkable successes with the FDA-approved proteasome inhibitors bortezomib (Velcade®) and carfilzomib
(Kyprolis®) have proved that the proteasome is an effective target for the treatment of multiple myeloma. In other
hematological malignancies, however, clinical trials of proteasome-targeting drugs have shown generally disappointing
results to date. Additionally, existing proteasome inhibitors have significant issues with toxicity, poor response rate, and
the emergence of resistance for many patients. A new generation of small-molecule therapies specifically targeting the
immunoproteasome may have the potential to overcome the drawbacks of bortezomib and carfilzomib in multiple
myeloma and to bring significant benefits of proteasome inhibitor therapies to many more patients. In this article, we
describe the potential of the immunoproteasome as a therapeutic target for hematological malignancies and the recent
progress in the development of useful immunoproteasome inhibitors.
