An image guided small animal radiation therapy platform (SmART) to monitor glioblastoma progression and therapy response

Yahyanejad, Sanaz; Hoof, Stefan J van; Theys, Jan; Barbeau, L.; Granton, Patrick V.; Paesmans, Kim; Verhaegen, Frank; Vooijs, Marc

doi:10.1016/j.radonc.2015.06.020

Cited by 21 publications

(41 citation statements)

References 14 publications

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“…Previously, we have shown the rationale for using the 3D spheroid system to model clinical efficacy of combination treatments [20]. Consistently, in this study we have shown that in vitro screening of NOTCH inhibitors combined with chemo-radiation (GSI + TMZ + RT) using 3D spheroid system is a robust methodology to identify novel synergistic combination therapies for GBM that reflect in vivo response.…”

Section: Discussionsupporting

confidence: 73%

“…We previously determined that single dose RT of 8 Gy results in a significant but modest tumor growth delay compared to tumors that did not receive any irradiation [20], thereby providing a window of opportunity where the combined effects of RT and TMZ could be measured. One week post-implantation, mice were imaged with BioLuminescence Imaging (BLI) 3 ×/week.…”

Section: Resultsmentioning

confidence: 99%

“…One week post-implantation, mice were imaged with BioLuminescence Imaging (BLI) 3 ×/week. Contrast-enhanced micro-CT was also used to monitor tumor growth periodically as reported previously [20]. Upon confirmation of tumor growth by either BLI or micro-CT, mice were randomized into eight different treatment arms.…”

Section: Resultsmentioning

confidence: 99%

“…An example of the parallel-opposed radiation treatment in sagittal, axial and coronal planes (Figure 4A–4C) and the dose volume histograms (DVHs) for all irradiated mice is shown (Figure 4D). These DVHs demonstrate that a highly uniform dose distribution across the tumor volume is achieved at the desired prescription dose of 8 Gy [20]. …”

Section: Resultsmentioning

confidence: 99%

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NOTCH blockade combined with radiation therapy and temozolomide prolongs survival of orthotopic glioblastoma

et al. 2016

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Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. The current standard of care includes surgery followed by radiotherapy (RT) and chemotherapy with temozolomide (TMZ). Treatment often fails due to the radiation resistance and intrinsic or acquired TMZ resistance of a small percentage of cells with stem cell-like behavior (CSC). The NOTCH signaling pathway is expressed and active in human glioblastoma and NOTCH inhibitors attenuate tumor growth in vivo in xenograft models. Here we show using an image guided micro-CT and precision radiotherapy platform that a combination of the clinically approved NOTCH/γ-secretase inhibitor (GSI) RO4929097 with standard of care (TMZ + RT) reduces tumor growth and prolongs survival compared to dual combinations. We show that GSI in combination with RT and TMZ attenuates proliferation, decreases 3D spheroid growth and results into a marked reduction in clonogenic survival in primary and established glioma cell lines. We found that the glioma stem cell marker CD133, SOX2 and Nestin were reduced following combination treatments and NOTCH inhibitors albeit in a different manner. These findings indicate that NOTCH inhibition combined with standard of care treatment has an anti-glioma stem cell effect which provides an improved survival benefit for GBM and encourages further translational and clinical studies.

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Section: Discussionsupporting

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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NOTCH blockade combined with radiation therapy and temozolomide prolongs survival of orthotopic glioblastoma

et al. 2016

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“…Orthotopic models are encouraged. One example study of effectively utilizing small animal-targeted irradiation in an orthotopic model is that of Yahyanejad et al, 43 who used U87MG glioblastoma cells orthotopically injected into the mouse brain. After CT-documented growth, tumours were irradiated using a partial brain technique conformal to the tumour.…”

Section: Advances In Mouse Models-how To Fill the "Translational Gap"?mentioning

confidence: 99%

Tumour and normal tissue radiobiology in mouse models: how close are mice to mini-humans?

Koontz¹,

Verhaegen²,

Ruysscher³

2017

BJR

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Animal modelling is essential to the study of radiobiology and the advancement of clinical radiation oncology by providing preclinical data. Mouse models in particular have been highly utilized in the study of both tumour and normal tissue radiobiology because of their cost effectiveness and versatility. Technology has significantly advanced in preclinical radiation techniques to allow highly conformal image-guided irradiation of small animals in an effort to mimic human treatment capabilities. However, the biological and physical limitations of animal modelling should be recognized and considered when interpreting preclinical radiotherapy (RT) studies. Murine tumour and normal tissue radioresponse has been shown to vary from human cellular and molecular pathways. Small animal irradiation techniques utilize different anatomical boundaries and may have different physical properties than human RT. This review addresses the difference between the human condition and mouse models and discusses possible strategies for future refinement of murine models of cancer and radiation for the benefit of both basic radiobiology and clinical translation.

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Combination Drug Therapy of Glioblastoma: Lessons from 3D In Vitro Models and the Roadmap for Future Research

Vaezzadeh,

Kachooei,

Krishnamurthy

et al. 2023

Advanced Therapeutics

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Combination drug therapy addresses the auxiliary cancer pathways of the tumor progression unaffected by the standard adjuvant treatments such as radio‐ and chemotherapy. It is a particularly attractive strategy to improve the treatment outcomes and the quality of life in patients with the deadliest brain cancer, glioblastoma (GB). Testing of combination drug treatment protocols requires reliable, efficient, and biologically accurate preclinical testbeds applicable before the transition to clinical trials. The 3D in vitro models of GB are a promising platform for pharmacological research. However, there is notable methodological uncertainty and a highly scattered data landscape regarding drug testing in 3D in vitro models of GB. In particular, it is not completely clear how to mimic clinically relevant dozing and schedule of the main chemotherapy drug for GB, temozolomide (TMZ) in 3D in vitro GB models. Here, the authors carefully explore the available literature on the application of TMZ in 3D in vitro models of GB, both as a sole agent and in combination with other medications. The joint analysis of the tumor modeling approaches, the employed assays, and the obtained treatment responses provided in this review may be used as a roadmap for future research in combination treatments of GB.

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An image guided small animal radiation therapy platform (SmART) to monitor glioblastoma progression and therapy response

Cited by 21 publications

References 14 publications

NOTCH blockade combined with radiation therapy and temozolomide prolongs survival of orthotopic glioblastoma

NOTCH blockade combined with radiation therapy and temozolomide prolongs survival of orthotopic glioblastoma

Tumour and normal tissue radiobiology in mouse models: how close are mice to mini-humans?

Combination Drug Therapy of Glioblastoma: Lessons from 3D In Vitro Models and the Roadmap for Future Research

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