Interstitial chemotherapy for malignant glioma: Future prospects in the era of multimodal therapy

Mangraviti, Antonella; Tyler, Betty; Brem, Henry

doi:10.4103/2152-7806.151345

Cited by 17 publications

(4 citation statements)

References 65 publications

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“…65,66,79 Gliadel® is an FDA-approved, biodegradable, polyanhydride-based polymer wafer containing the alkylating agent carmustine (BCNU: N,N′-bis-[2-chloroethyl]-N-nitrosurea), a chemotherapeutic that exhibits high hematologic cell toxicity when administered systemically. 79-81 These wafers, which are ∼1.5 cm in diameter, are implanted into the surgical resection cavity following tumor excision. Gliadel® wafer implantation produces a small but significant improvement in median patient survival time compared to placebo wafers (∼2 months).…”

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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“…Another strategy employed clinically is the slow physical degradation of the polymer to release payloads, as seen in the FDA-approved Gliadel wafer. Nonetheless, this approach can affect drug distribution profiles since the polymer doesn't maintain the same contact with the tissue over time 4,5,37,67,75 And, despite its extended release capabilities, Oncogel, too, deteriorates over time. Ultimately, this results in similar challenges as those observed with Gliadel.…”

Section: Discussionmentioning

confidence: 99%

Versatile Tissue-Injectable Hydrogels with Extended Hydrolytic Release of Bioactive Protein Therapeutics

Nealy,

Reed,

Adelmund

et al. 2023

Preprint

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Hydrogels generally have broad utilization in healthcare due to their tunable structures, high water content, and inherent biocompatibility. FDA-approved applications of hydrogels include spinal cord regeneration, skin fillers, and local therapeutic delivery. Drawbacks exist in the clinical hydrogel space, largely pertaining to inconsistent therapeutic exposure, short-lived release windows, and difficulties inserting the polymer into tissue. In this study, we engineered injectable, biocompatible hydrogels that function as a local protein therapeutic depot with a high degree of user-customizability. We showcase a PEG-based hydrogel functionalized with bioorthogonal strain-promoted azide-alkyne cycloaddition (SPAAC) handles for its polymerization and functionalization with a variety of payloads. Small-molecule and protein cargos, including chemokines and antibodies, were site-specifically modified with hydrolysable azidoesters of varying hydrophobicity via direct chemical conjugation or sortase-mediated transpeptidation. These hydrolysable esters afforded extended releases of payloads linked to our hydrogels, with timescales spanning days to months dependent on ester hydrophobicity. Injected hydrogels polymerize in situ and remain in tissue over extended periods of time. Hydrogel-delivered protein payloads elicit biological activity after being modified with SPAAC-compatible linkers, as demonstrated by the successful recruitment of murine T-cells to a mouse melanoma model by hydrolytically released murine CXCL10. These results highlight a highly versatile, customizable hydrogel-based delivery system for local delivery of protein therapeutics with payload release profiles appropriate for a variety of clinical needs.

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“…However, Doxorubicin is not commonly used in clinical glioma chemotherapy regimens due to it is less capable to pass through the blood–brain barrier. Nevertheless, development in interstitial chemotherapy makes it possible to deliver drugs directly at the site of brain tumor 50 , which provides more therapeutic options for patients who are suffering from brain tumor. Our study shows that knockdown of MINA53 sensitized glioblastoma cells to the genotoxic drug Doxorubicin, which gives more support for gene and drug combination therapeutics and may help to further improve the efficacy of glioblastoma interstitial chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

MINA53 deficiency leads to glioblastoma cell apoptosis via inducing DNA replication stress and diminishing DNA damage response

et al. 2018

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MYC-induced nuclear antigen (MINA53) is a JmjC (jumonji C domain)-containing protein, which is highly expressed in many cancers including glioblastoma. We have revealed in our previous report that MINA53 is a poor prognostic indicator for glioblastoma patients, and knockdown of MINA53 could reduce glioblastoma malignancy. In this study, we found that MINA53 knockdown could decrease the DNA replication initiation in glioblastoma cells. Through further investigations, we revealed that MINA53 could regulate the expression of the CDC45-MCM-GINS (CMG) complex genes, which are vital for DNA replication initiation. Knockdown of MINA53 reduced the CMG genes expression and thus induced DNA replication stress and DNA damage. Furthermore, MINA53 knockdown diminished DNA damage response (DDR) by reducing the ATM/ATR-H2AX pathway activity and finally led glioblastoma cells to apoptosis and death. We further applied a genotoxic drug Doxorubicin and found that MINA53 deficiency sensitized glioblastoma cells to Doxorubicin. Our study reveals that MINA53 is involved in DNA replication initiation and DNA damage response, and provides support for MINA53 as a novel and potential therapeutic target for glioblastoma treatment.

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Interstitial chemotherapy for malignant glioma: Future prospects in the era of multimodal therapy

Cited by 17 publications

References 65 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

Versatile Tissue-Injectable Hydrogels with Extended Hydrolytic Release of Bioactive Protein Therapeutics

MINA53 deficiency leads to glioblastoma cell apoptosis via inducing DNA replication stress and diminishing DNA damage response

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