Proteasome inhibitors in acute leukemia.

Abstract

Proteasome inhibition has been recognized as a novel treatment modality in hematologic malignancies. Initially, the reversible proteasome inhibitor bortezomib demonstrated efficacy in multiple myeloma (MM), which supported its approval for relapsed and refractory MM in 2003. Later on, carfilzomib, a next-generation irreversible proteasome inhibitor was approved by the US FDA in July 2012 for relapsed/refractory MM. Currently, several other proteasome inhibitors are undergoing preclinical and clinical evaluation. The successes of proteasome inhibitors in MM are now being translated to other hematologic malignancies, including acute leukemia. The first clinical studies with bortezomib in leukemia revealed promising clinical activity, particularly when combined with conventional chemotherapeutics. In this review the position of proteasome inhibitors in acute leukemia treatment is summarized and discussed. Special focus is also attributed to immunoproteasome inhibitors. As a future perspective, it is anticipated that proteasome inhibitors may prove to be of added value in therapeutic interventions for acute leukemia.

• Authors: Denise Niewerth, Ilse Dingjan, Jacqueline Cloos, Gerrit Jansen, Gertjan Kaspers
• Journal: Expert review of anticancer therapy (Expert Rev Anticancer Ther) Vol. 13 Issue 3 Pg. 327-37 (Mar 2013) ISSN: 1744-8328 [Electronic] England
• PMID: 23477519 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• Proteasome Inhibitors

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Clinical Trials as Topic
• Drug Evaluation, Preclinical
• Humans
• Leukemia (drug therapy, enzymology)
• Proteasome Inhibitors (pharmacology, therapeutic use)
• Randomized Controlled Trials as Topic