Polymeric drug delivery for the treatment of glioblastoma

Wait, Scott D.; Prabhu, Roshan S.; Burri, Stuart H.; Atkins, Tyler; Asher, Anthony L.

doi:10.1093/neuonc/nou360

Cited by 71 publications

(68 citation statements)

References 105 publications

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“…Gliadel® wafer implantation produces a small but significant improvement in median patient survival time compared to placebo wafers (∼2 months). 79,80,82 For this form of interstitial chemotherapy, drug delivery is mediated by diffusion; consequently, Gliadel® efficacy is likely limited, at least in part, by the inability to achieve therapeutic drug concentrations more than a few millimeters beyond the immediate tumor resection margin. 80,83 …”

Section: Introductionmentioning

confidence: 99%

The TWEAK receptor Fn14 is a potential cell surface portal for targeted delivery of glioblastoma therapeutics

et al. 2015

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Fibroblast growth factor-inducible 14 (Fn14; TNFRSF12A) is the cell surface receptor for the tumor necrosis factor (TNF) family member TNF-like weak inducer of apoptosis (TWEAK). The Fn14 gene is normally expressed at low levels in healthy tissues but expression is significantly increased after tissue injury and in many solid tumor types, including glioblastoma (GB; formerly referred to as ‘glioblastoma multiforme’ or GBM). GB is the most common and aggressive primary malignant brain tumor, and the current standard-of-care therapeutic regimen has a relatively small impact on patient survival, primarily because glioma cells have an inherent propensity to invade into normal brain parenchyma, which invariably leads to tumor recurrence and patient death. Despite major, concerted efforts to find new treatments, a new GB therapeutic that improves survival has not been introduced since 2005. In this review article, we summarize studies indicating that (i) Fn14 gene expression is low in normal brain tissue but up-regulated in advanced brain cancers and, in particular, in GB tumors exhibiting the mesenchymal molecular subtype, (ii) Fn14 expression can be detected in glioma cells residing in both the tumor core and invasive rim regions, with the maximal levels found in the invading glioma cells located within normal brain tissue, and (iii) TWEAK:Fn14 engagement as well as Fn14 overexpression can stimulate glioma cell migration, invasion, and resistance to chemotherapeutic agents in vitro. We also discuss two new therapeutic platforms that are currently in development that leverage Fn14 overexpression in GB tumors as a way to deliver cytotoxic agents to the glioma cells remaining after surgical resection while sparing normal healthy brain cells.

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Section: Introductionmentioning

confidence: 99%

The TWEAK receptor Fn14 is a potential cell surface portal for targeted delivery of glioblastoma therapeutics

et al. 2015

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“…Subsequent to the approval of temozolomide (TMZ) by the Food and Drug Administration in 1999, post-operative radiotherapy (RT) combined with TMZ chemotherapy has been developed as the standard therapy for newly diagnosed GBM (24). The median survival length subsequent to treatment with RT plus TMZ was 14.6 months compared with 12.1 months for RT alone (10,23,25). Therefore, the exploration of novel agents that could be used alone or combined with TMZ to improve the outcome of GBM is required.…”

Section: Discussionmentioning

confidence: 99%

PT93, a novel caffeic acid amide derivative, suppresses glioblastoma cells migration, proliferation and MMP-2/−9 expression

Liu

et al. 2017

Oncology Letters

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Abstract. Glioblastoma multiforme (GBM) is the most malignant type of primary brain tumor in adults and can diffusely infiltrate adjacent normal tissue. GBM is therefore rarely cured by surgery or radiation therapy. Matrix metalloproteinases (MMPs) are involved in tissue remodeling and numerous other physiological progresses. The MMPs MMP-2 and MMP-9 are associated with the invasion ability of GBM. PT93 is a novel caffeic acid amide derivative that was first synthesized in 2013. In the present study, the human GBM T98G, U87 and U251 cell lines and the normal mouse neuron HT22 cell line were used to investigate the anticancer and cytotoxic effects of PT93 in vitro. The cytotoxicity of PT93 was measured using MTT and lactate dehydrogenase assays. The anti-proliferation effect was tested using a cell colony formation assay. Gelatin zymography analysis and a scratch test were used to investigate the anti-migration mechanism of PT93. Western blot analysis was used to measure the expression of MMP-2/-9. The experimental results showed that PT93 suppressed the proliferation of T98G cells, and showed cytotoxicity effects at high concentration in T98G, U87, U251 and HT22 cell lines. Furthermore, PT93 limited the migration ability of the cells and inhibited the extracellular MMP-2 and MMP-9 activity of T98G and U251 cells. Finally, the present study confirmed that PT93 affects the level of MMP-2/-9 expression in T98G cells in a concentration-dependent manner. The present study indicates that PT93, as a novel caffeic acid amide derivative, may be used in the treatment of GBM.

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“…Approved for treatment of a series of metastatic cancers, preliminary results in glioblastoma have so far shown an increase in progression‐free survival, but not in overall survival . Less conventional strategies that have also obtained FDA approval for the treatment of recurrent glioblastoma include carmustine biodegradable wafers, which are placed at the site of the resected tumor to release chemotherapy locally, and transcutaneous delivery of low‐intensity alternating electric fields, aimed at disrupting the mitotic spindle of dividing cancer cells . In conclusion, current therapeutic avenues for glioblastoma have been focused on tackling tumor cell proliferation by multiple different angles, but the limited impact on overall survival prompts the development of new strategies.…”

Section: Glioblastomamentioning

confidence: 99%

Co‐inhibitory blockade while preserving tolerance: checkpoint inhibitors for glioblastoma

Lucca

Hafler

2017

Immunological Reviews

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Summary The introduction of immunotherapy with checkpoint receptor blockade has changed the treatment of advanced cancers, at times inducing prolonged remission. Nevertheless, the success rate of the approach is variable across patients and different tumor types, and treatment is often accompanied by severe immune-related side effects, suggesting the importance of co-inhibitory pathway for both prevention of autoimmunity and failure of tumor rejection. A better understanding of how to uncouple anti-tumor activity from loss of self-tolerance is necessary in order to increase the therapeutic efficacy of checkpoint immunotherapy. In this review, we describe basic concepts of T cell exhaustion that occur in cancer, highlighting the role of co-inhibitory receptors in contributing to this process while preventing immunopathology. By providing an overview of the current therapeutic success and immune-related burden of secondary effects of checkpoint immunotherapy, we illustrate the “double-edged sword” related to interference with immune-regulatory pathways. Finally, since achieving tumor rejection while preserving self-tolerance is particularly important for the central nervous system, we analyze the case for checkpoint immunotherapy in glioblastoma, the most common adult brain tumor.

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Polymeric drug delivery for the treatment of glioblastoma

Cited by 71 publications

References 105 publications

The TWEAK receptor Fn14 is a potential cell surface portal for targeted delivery of glioblastoma therapeutics

The TWEAK receptor Fn14 is a potential cell surface portal for targeted delivery of glioblastoma therapeutics

PT93, a novel caffeic acid amide derivative, suppresses glioblastoma cells migration, proliferation and MMP-2/−9 expression

Co‐inhibitory blockade while preserving tolerance: checkpoint inhibitors for glioblastoma

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