Proteasome inhibitors in glioblastoma

Huang, Wenjuan; Chen, Weiwei; Zhang, Xia

doi:10.3892/ol.2017.5585

Cited by 7 publications

(4 citation statements)

References 56 publications

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“…This therapy is able to increase apoptosis levels in preclinical brain tumor assays. Moreover, clinical trials using proteasome inhibitors in combination strategies are being tested to maximize therapeutic efficacy and limit toxicity [ 263 ]. Bortezomib is studied in combination with TMZ and/or radiation, or with an inhibitor of histone deacetylase.…”

Section: Results-glioblastoma Targeted Therapiesmentioning

confidence: 99%

A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials

Silva

Mercier

Étienne-Selloum

et al. 2021

Cancers

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Glioblastoma (GBM), the most frequent and aggressive glial tumor, is currently treated as first line by the Stupp protocol, which combines, after surgery, radiotherapy and chemotherapy. For recurrent GBM, in absence of standard treatment or available clinical trials, various protocols including cytotoxic drugs and/or bevacizumab are currently applied. Despite these heavy treatments, the mean overall survival of patients is under 18 months. Many clinical studies are underway. Based on clinicaltrials.org and conducted up to 1 April 2020, this review lists, not only main, but all targeted therapies in phases II-IV of 257 clinical trials on adults with newly diagnosed or recurrent GBMs for the last twenty years. It does not involve targeted immunotherapies and therapies targeting tumor cell metabolism, that are well documented in other reviews. Without surprise, the most frequently reported drugs are those targeting (i) EGFR (40 clinical trials), and more generally tyrosine kinase receptors (85 clinical trials) and (ii) VEGF/VEGFR (75 clinical trials of which 53 involving bevacizumab). But many other targets and drugs are of interest. They are all listed and thoroughly described, on an one-on-one basis, in four sections related to targeting (i) GBM stem cells and stem cell pathways, (ii) the growth autonomy and migration, (iii) the cell cycle and the escape to cell death, (iv) and angiogenesis.

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Section: Results-glioblastoma Targeted Therapiesmentioning

confidence: 99%

A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials

Silva

Mercier

Étienne-Selloum

et al. 2021

Cancers

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“…The subsequent inhibition of NFκB with proteasome inhibitors enhanced the MGCD0103-induced death of Hodgkin lymphoma cells ( 101 ). The combination of HDACi with proteasome inhibitors may additionally be used to treat glioblastomas in order to maximize the therapeutic efficacy and limit the toxicity associated with using proteasome inhibitors as a single agent in this disease ( 102 ). Clinical trials with bortezomib in combination with either vorinostat as a third-line treatment in advanced NSCLC ( identifier: NCT00798720) or with panobinostat for the treatment of relapsed/refractory T-cell lymphoma or NK/T-cell lymphoma following conventional chemotherapy failure ( identifier: NCT00901147) have been completed.…”

Section: Combining Hdaci and Proteasome Inhibitorsmentioning

confidence: 99%

Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi

2018

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Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, HDACi have shown limited success in treating solid tumors. The combination of HDACi with standard chemotherapeutic drugs has demonstrated promising anticancer effects in both preclinical and clinical studies. In this review, we summarize the research thus far on HDACi in combination therapy, with other anticancer agents and their translation into preclinical and clinical studies. We additionally highlight the side effects associated with HDACi in cancer therapy and discuss potential biomarkers to either select or predict a patient’s response to these agents, in order to limit the off-target toxicity associated with HDACi.

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“…132,133 Similarly, proteasome inhibitors which have demonstrated a potent anti-tumor effect on brain cancer models in vitro offered limited clinical benefits due to their poor affinity with the BBB. 134 These examples suggest that treatment of CNS pathologies requires new delivery systems rather than new drugs.…”

Section: Enhancing Drug Transport Across the Bbb Via Nanocarrier-mediated Drug Deliverymentioning

confidence: 99%

In vitro models of molecular and nano-particle transport across the blood-brain barrier

et al. 2018

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The blood-brain barrier (BBB) is the tightest endothelial barrier in humans. Characterized by the presence of tight endothelial junctions and adherens junctions, the primary function of the BBB is to maintain brain homeostasis through the control of solute transit across the barrier. The specific features of this barrier make for unique modes of transport of solutes, nanoparticles, and cells across the BBB. Understanding the different routes of traffic adopted by each of these is therefore critical in the development of targeted therapies. In an attempt to move towards controlled experimental assays, multiple groups are now opting for the use of microfluidic systems. A comprehensive understanding of bio-transport processes across the BBB in microfluidic devices is therefore necessary to develop targeted and efficient therapies for a host of diseases ranging from neurological disorders to the spread of metastases in the brain.

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Proteasome inhibitors in glioblastoma

Cited by 7 publications

References 56 publications

A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials

A Systematic Review of Glioblastoma-Targeted Therapies in Phases II, III, IV Clinical Trials

Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi

In vitro models of molecular and nano-particle transport across the blood-brain barrier

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