International experience in the development of patient-derived xenograft models of diffuse intrinsic pontine glioma

Tsoli, Maria; Shen, Han; Mayoh, Chelsea; Franshaw, Laura; Ehteda, Anahid; Upton, Dannielle; Carvalho, Diana; Vinci, Maria; Meel, Michaël H.; Vuurden, Dannis G. van; Plessier, Alexander; Castel, David; Drissi, Rachid; Farrell, Michael; Cryan, Jane; Crimmins, Darach; Caird, John; Pears, Jane; Francis, Stephanie; Ludlow, Louise E.; Carai, Andrea; Mastronuzzi, Angela; Liu, Bing; Hansford, Jordan R.; Gottardo, Nicholas G.; Hassall, Tim; Kirby, Maria; Fouladi, Maryam; Hawkins, Cynthia; Monje, Michelle; Grill, Jacques; Jones, Chris; Hulleman, Esther; Ziegler, David S.

doi:10.1007/s11060-018-03038-2

Cited by 33 publications

(23 citation statements)

References 31 publications

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“…Patient-derived cells, animal models, and genetic engineering are paving new roads toward meaningful treatment. 3,43,49,66 In 1993, Leland Albright presented a convincing case against all operative intervention for DIPG given the diagnostic capacity of MRI, unacceptable morbidity of resection, and lack of utility of tissue biopsy. 1 However, in the intervening decades, the increased safety and feasibility of stereotactic biopsy, together with research developments of clinical significance, command reexamination of this stance.…”

Section: Role Of Neurosurgery In Dipg Treatment and Biopsymentioning

confidence: 99%

Progress in diffuse intrinsic pontine glioma: advocating for stereotactic biopsy in the standard of care

Williams

Young

Vitanza

et al. 2020

Neurosurgical Focus

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Diffuse intrinsic pontine glioma (DIPG) is a universally fatal pediatric brainstem tumor affecting approximately 300 children in the US annually. Median survival is less than 1 year, and radiation therapy has been the mainstay of treatment for decades. Recent advances in the biological understanding of the disease have identified the H3K27M mutation in nearly 80% of DIPGs, leading to the 2016 WHO classification of diffuse midline glioma H3K27M-mutant, a grade IV brainstem tumor. Developments in epigenetic targeting of transcriptional tendencies have yielded potential molecular targets for clinical trials. Chimeric antigen receptor T cell therapy has also shown preclinical promise. Recent clinical studies, including prospective trials, have demonstrated the safety and feasibility of pediatric brainstem biopsy in the setting of DIPG and other brainstem tumors. Given developments in the ability to analyze DIPG tumor tissue to deepen biological understanding of this disease and develop new therapies for treatment, together with the increased safety of stereotactic brainstem biopsy, the authors present a case for offering biopsy to all children with suspected DIPG. They also present their standard operative techniques for image-guided, frameless stereotactic biopsy.

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Section: Role Of Neurosurgery In Dipg Treatment and Biopsymentioning

confidence: 99%

Progress in diffuse intrinsic pontine glioma: advocating for stereotactic biopsy in the standard of care

Williams

Young

Vitanza

et al. 2020

Neurosurgical Focus

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“…Despite over 250 clinical trials with different therapeutic agents there has been no improvement in the dismal prognosis of DIPG 6 with focal irradiation still remaining the standard treatment. Over the past decade, the implementation of autopsy and biopsy sampling has increased our understanding of the molecular landscape of DIPG tumors 7,8 . Nearly 80% of DIPG tumors harbor an H3K27M mutation leading to loss of H3K27 trimethylation and aberrant gene expression.…”

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confidence: 99%

Dual targeting of polyamine synthesis and uptake in diffuse intrinsic pontine gliomas

et al. 2021

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Diffuse intrinsic pontine glioma (DIPG) is an incurable malignant childhood brain tumor, with no active systemic therapies and a 5-year survival of less than 1%. Polyamines are small organic polycations that are essential for DNA replication, translation and cell proliferation. Ornithine decarboxylase 1 (ODC1), the rate-limiting enzyme in polyamine synthesis, is irreversibly inhibited by difluoromethylornithine (DFMO). Herein we show that polyamine synthesis is upregulated in DIPG, leading to sensitivity to DFMO. DIPG cells compensate for ODC1 inhibition by upregulation of the polyamine transporter SLC3A2. Treatment with the polyamine transporter inhibitor AMXT 1501 reduces uptake of polyamines in DIPG cells, and co-administration of AMXT 1501 and DFMO leads to potent in vitro activity, and significant extension of survival in three aggressive DIPG orthotopic animal models. Collectively, these results demonstrate the potential of dual targeting of polyamine synthesis and uptake as a therapeutic strategy for incurable DIPG.

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“…In particular, the availability of mouse and PDX models of DIPG have elevated the preclinical trials that can be carried out for this deadly disease. A recent survey of attempts to generate DIPG PDX and cell lines found that an encouraging 40–85% were successful across implant and culture models for both autopsy and biopsy material . Besides the EZH2 inhibitors discussed previously, small molecules targeting multiple other pathways have been tested using these models and proposed as potential therapeutics or tool compounds.…”

Section: Therapeutic Outlookmentioning

confidence: 99%

Invited Review: Emerging functions of histone H3 mutations in paediatric diffuse high‐grade gliomas

Kasper

Baker

2020

Neuropathology Appl Neurobio

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2020) Neuropathology and Applied Neurobiology 46, 73-85 Emerging functions of histone H3 mutations in paediatric diffuse high-grade gliomas Paediatric diffuse high-grade gliomas (pHGG) are rare, but deadly tumours. The discovery of recurrent mutations in the tail of histone H3, changing lysine 27 to methionine, or glycine 34 to arginine or valine, has illuminated a critical role for epigenetic dysregulation in the aetiology of childhood gliomas and opened new avenues of exploration that have resulted in numerous advances for the field. In this review, we describe the current models of H3K27M mutant cancer that are available to the research community and the insights they have provided on tumour biology and the epigenetic and transcriptional effects of histone mutations. We also review the current understanding of the H3G34R/V mutation and the therapeutic outlook for the treatment of pHGG.

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International experience in the development of patient-derived xenograft models of diffuse intrinsic pontine glioma

Cited by 33 publications

References 31 publications

Progress in diffuse intrinsic pontine glioma: advocating for stereotactic biopsy in the standard of care

Progress in diffuse intrinsic pontine glioma: advocating for stereotactic biopsy in the standard of care

Dual targeting of polyamine synthesis and uptake in diffuse intrinsic pontine gliomas

Invited Review: Emerging functions of histone H3 mutations in paediatric diffuse high‐grade gliomas

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