The role of proteasome inhibition in the treatment of malignant and non-malignant hematologic disorders

ABSTRACT

Introduction: Proteasome inhibitors have garnered interest as novel chemotherapeutic agents based on their ability to inhibit the growth of cancer cells by altering the balance of intracellular proteins. Initial clinical trials of this drug class focused on bortezomib, a reversible inhibitor of the 20S proteasome, with promising results for the treatment of adult hematologic malignancies, including multiple myeloma and non-Hodgkin lymphoma.

Areas covered: This article will review the use of bortezomib and other proteasome inhibitors in both adult and pediatric populations, with a focus on their use in pediatrics.

Expert commentary: Bortezomib moved into the pediatric oncology arena with encouraging results in multiple early phase trials for relapsed acute lymphoblastic leukemia and acute myeloid leukemia. Bortezomib is also being studied in the treatment of non-malignant disorders, including antibody-mediated allograft rejection, graft-versus-host disease, and autoimmune cytopenias. The numerous applications of bortezomib have inspired the development of second-generation proteasome inhibitors.

KEYWORDS:

• Bortezomib
• proteasome
• NF-κB
• acute lymphoblastic leukemia
• multiple myeloma
• autoimmune disease

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.