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.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Roth P,Mason WP,Richardson PG,Weller Mdoi
10.1080/13543784.2020.1803827subject
Has Abstractpub_date
2020-10-01 00:00:00pages
1133-1141issue
10eissn
1354-3784issn
1744-7658journal_volume
29pub_type
杂志文章abstract::Transcription factors are proteins that regulate gene transcription and expression. In many cases of acute leukaemia chromosomal aberrations are translocations of transcription factors which change their expression and induce the leukaemic phenotype. These abnormal transcription factors are tumour-specific and can be ...
journal_title:Expert opinion on investigational drugs
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journal_title:Expert opinion on investigational drugs
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journal_title:Expert opinion on investigational drugs
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journal_title:Expert opinion on investigational drugs
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journal_title:Expert opinion on investigational drugs
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doi:10.1517/13543784.2012.632408
更新日期:2012-01-01 00:00:00
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journal_title:Expert opinion on investigational drugs
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pub_type: 杂志文章,评审
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journal_title:Expert opinion on investigational drugs
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doi:10.1517/13543784.2014.986264
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