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.

• Authors: Rebecca Citrin, Jessica B Foster, David T Teachey
• Journal: Expert review of hematology (Expert Rev Hematol) Vol. 9 Issue 9 Pg. 873-89 (Sep 2016) ISSN: 1747-4094 [Electronic] England
• PMID: 27447436 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Proteasome Inhibitors
• Bortezomib
• Proteasome Endopeptidase Complex

Topics

• Age Factors
• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Bortezomib (pharmacology, therapeutic use)
• Clinical Trials as Topic
• Drug Evaluation, Preclinical
• Hematologic Diseases (diagnosis, drug therapy, metabolism)
• Hematologic Neoplasms (diagnosis, drug therapy, metabolism, mortality)
• Humans
• Proteasome Endopeptidase Complex (metabolism)
• Proteasome Inhibitors (pharmacology, therapeutic use)
• Signal Transduction
• Treatment Outcome