Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

Neubeck, Cläre von; Seidlitz, Annekatrin; Kitzler, Hagen H.; Beuthien‐Baumann, Bettina; Krause, Mechthild

doi:10.1259/bjr.20150354

Cited by 56 publications

(43 citation statements)

References 135 publications

(154 reference statements)

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“…Clinically, TMZ is among the lead chemotherapeutic agents used for the treatment of nervous system cancers, particularly malignant brain tumors, because of its bioavail-ability and limited toxicity (32). However, a caveat of its efficacy has been intrinsic and acquired resistance as a result in part of activating pro-survival signaling mediators (33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Microtubule actin cross-linking factor 1, a novel target in glioblastoma

Afghani

Mehta

Wang

et al. 2016

International Journal of Oncology

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Genetic heterogeneity is recognized as a major contributing factor of glioblastoma resistance to clinical treatment modalities and consequently low overall survival rates. This genetic diversity results in variations in protein expression, both intratumorally and between individual glioblastoma patients. In this regard, the spectraplakin protein, microtubule actin cross-linking factor 1 (MACF1), was examined in glioblastoma. An expression analysis of MACF1 in various types of brain tumor tissue revealed that MACF1 was predominately present in grade III-IV astroctyomas and grade IV glioblastoma, but not in normal brain tissue, normal human astrocytes and lower grade brain tumors. Subsequent genetic inhibition experiments showed that suppression of MACF1 selectively inhibited glioblastoma cell proliferation and migration in cell lines established from patient derived xenograft mouse models and immortalized glioblastoma cell lines that were associated with downregulation of the Wnt-signaling mediators, Axin1 and β-catenin. Additionally, concomitant MACF1 silencing with the chemotherapeutic agent temozolomide (TMZ) used for the clinical treatment of glioblastomas cooperatively reduced the proliferative capacity of glioblastoma cells. In conclusion, the present study represents the first investigation on the functional role of MACF1 in tumor cell biology, as well as demonstrates its potential as a unique biomarker that can be targeted synergistically with TMZ as part of a combinatorial therapeutic approach for the treatment of genetically multifarious glioblastomas.

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Section: Discussionmentioning

confidence: 99%

Microtubule actin cross-linking factor 1, a novel target in glioblastoma

Afghani

Mehta

Wang

et al. 2016

International Journal of Oncology

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“…108 Progressive disease is treated with antiangiogenic agents (eg, bevacizumab) and/or nitrosourea alkylating agents (eg, lomustine). 109,110 Gliomas of lower grades are treated with resection and some combination of chemoradiotherapy as adjuvant therapy or for recurrence. 111,112 Treatment of metastases primarily depends on their number, with solitary lesions amenable to resection whereas multiple lesions are often treated radiosurgically.…”

Section: Imaging Of Treatment Responsementioning

confidence: 99%

“…Other advanced techniques currently being investigated include nuclear imaging agents, although their use in broad clinical practice is limited and beyond the scope of this review. 109,147,148 …”

Section: Imaging Of Treatment Responsementioning

confidence: 99%

Current Clinical Brain Tumor Imaging

2017

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Neuroimaging plays an ever evolving role in the diagnosis, treatment planning, and post-therapy assessment of brain tumors. This review provides an overview of current magnetic resonance imaging (MRI) methods routinely employed in the care of the brain tumor patient. Specifically, we focus on advanced techniques including diffusion, perfusion, spectroscopy, tractography, and functional MRI as they pertain to noninvasive characterization of brain tumors and pretreatment evaluation. The utility of both structural and physiological MRI in the post-therapeutic brain evaluation is also reviewed with special attention to the challenges presented by pseudoprogression and pseudoresponse.

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“…Standard-of-care therapies for primary brain tumors include radiation therapy (RT) [Murphy et al, 2015;von Neubeck et al, 2015]. Oxidative stress effects of RT can damage normal tissue and lead to progressive neurobehavioral impairments [Greene-Schloesser et al, 2012;Attia et al, 2014].…”

Section: Introductionmentioning

confidence: 99%

Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n‐butoxyethylpyridylporphyrin‐based redox modifier

Weitzel

Tovmasyan

Ashcraft

et al. 2016

Environ and Mol Mutagen

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Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy-induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have recently shown that MnTnBuOE-2-PyP(5+) (Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium -2-yl)porphyrin) rescued RT-induced white matter damage in cranially-irradiated mice. Radiotherapy is not used in isolation for treatment of brain tumors; temozolomide is the standard-of-care for adult glioblastoma, whereas cisplatin is often used for treatment of pediatric brain tumors. Therefore, we evaluated the brain radiation mitigation ability of MnTnBuOE-2-PyP(5+) after either temozolomide or cisplatin was used singly or in combination with 10 Gy RT. MnTnBuOE-2-PyP(5+) accumulated in brains at low nanomolar levels. Histological and neurobehavioral testing showed a drastic decrease (1) of axon density in the corpus callosum and (2) rotorod and running wheel performance in the RT only treatment group, respectively. MnTnBuOE-2-PyP(5+) completely rescued this phenotype in irradiated animals. In the temozolomide groups, temozolomide/ RT treatment resulted in further decreased rotorod responses over RT alone. Again, MnTnBuOE-2-PyP(5+) treatment rescued the negative effects of both temozolomide ± RT on rotorod performance. While the cisplatin-treated groups did not give similar results as the temozolomide groups, inclusion of MnTnBuOE-2-PyP(5+) did not negatively affect rotorod performance. Additionally, MnTnBuOE-2-PyP(5+) sensitized glioblastomas to either RT ± temozolomide in flank tumor models. Mice treated with both MnTnBuOE-2-PyP(5+) and radio-/chemo-therapy herein demonstrated brain radiation mitigation. MnTnBuOE-2-PyP(5+) may well serve as a normal tissue radio-/chemo-mitigator adjuvant therapy to standard brain cancer treatment regimens. Environ. Mol. Mutagen. 57:372-381, 2016. © 2016 Wiley Periodicals, Inc.

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Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

Cited by 56 publications

References 135 publications

Microtubule actin cross-linking factor 1, a novel target in glioblastoma

Microtubule actin cross-linking factor 1, a novel target in glioblastoma

Current Clinical Brain Tumor Imaging

Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n‐butoxyethylpyridylporphyrin‐based redox modifier

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