Proteasome inhibition for the treatment of glioblastoma.

Abstract

INTRODUCTION:

Glioblastoma is a primary brain tumor with a poor prognosis despite multimodal therapy including surgery, radiotherapy and alkylating chemotherapy. Novel therapeutic options are therefore urgently needed; however, there have been various drug failures in late-stage clinical development. The proteasome represents a key target for anti-cancer therapy as successfully shown in multiple myeloma and other hematologic malignancies.

AREAS COVERED:

This review article summarizes the preclinical and clinical development of proteasome inhibitors in the context of glioblastoma.

EXPERT OPINION:

Early clinical trials with bortezomib ended with disappointing results, possibly because this agent does not cross the blood-brain barrier. In contrast to bortezomib and other proteasome inhibitors, marizomib is a novel drug that displays strong inhibitory properties on all enzymatic subunits of the proteasome and, most importantly, crosses the blood-brain barrier, making it a potentially very active novel agent against intrinsic brain tumors. While preclinical studies have demonstrated significant anti-glioma activity, its clinical benefit has yet to be proven. Exploiting the biological effects of proteasome inhibitors in combination with other therapeutic strategies may represent a key next step in their clinical development.

• Authors: Patrick Roth, Warren P Mason, Paul G Richardson, Michael Weller
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 29 Issue 10 Pg. 1133-1141 (Oct 2020) ISSN: 1744-7658 [Electronic] England
• PMID: 32746640 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Lactones
• Proteasome Inhibitors
• Pyrroles
• Bortezomib
• marizomib

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Bortezomib (administration & dosage, pharmacology)
• Brain Neoplasms (drug therapy, pathology)
• Drug Development
• Glioblastoma (drug therapy, pathology)
• Humans
• Lactones (administration & dosage, pharmacology)
• Proteasome Inhibitors (administration & dosage, pharmacology)
• Pyrroles (administration & dosage, pharmacology)