Proteasome inhibition for the treatment of glioblastoma. (2nd October 2020)

• Record Type: Journal Article
• Authors: Roth, Patrick; Mason, Warren P.; Richardson, Paul G.; Weller, Michael
• Is Part Of: Expert opinion on investigational drugs. Volume 29:Number 10(2020)
• Page Start: 1133
• Page End: 1141
• Publication Date: 2020-10-02
• Subjects: Glioblastoma -- brain tumor -- neuro-oncology -- chemotherapy -- proteasome -- marizomib -- bortezomib; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2020.1803827
• Languages: English
• ISSNs: 1354-3784

Abstract

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.