
Prof David Ziegler
@ProfDavidZieg
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Paediatric oncologist, clinical trials, neuro-oncology, precision medicine.
Sydney
Joined December 2019
RT @ISPNO2026: ISPNO 2026 now just over a year away! We will be attending PedSNO - come visit for a chance at complimentary registration!!….
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Great work from the team and hopefully a helpful resource for many @ JoVE
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RT @Dr_MMateos: Excited to see our work published in Neuro-Oncology @NeuroOnc. Large international study of 252 patients with #DMG #DIPG w….
pubmed.ncbi.nlm.nih.gov
Our study determined the prevalence of pathogenic germline variants in pediatric DMG, and suggests a role in tumorigenesis for a subset of patients.
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Thanks to all collaborators who helped assemble the largest cohort of DMG patients with germline sequencing. Helping us understand the cause and new DMG treatments: .Germline analysis of an international cohort of pediatric diffuse midline glioma patients
academic.oup.com
AbstractBackground. Factors that drive the development of diffuse midline gliomas (DMG) are unknown. Our study aimed to determine the prevalence of pathoge
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12: Thanks to funding from NHMRC, CINSW, Cancer Australia, Cure Brain Cancer, The DIPG Collaborative, The Cure Starts Now, Levi's Project, Benny Wills Fund.
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11: Thanks to all the patients and families who have supported this work through advice, encouragement, fund raising and allowing us to use their child's tumour samples - without which no research is possible.
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10: We have discovered fenretinide is one of those treatments, but we need effective combinations to make it more active. We have new therapeutic vulnerabilities that will help us in our search for a cure.
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9: We have had too many failed trials, and we need to ensure that the treatments with real promise are prioritised for our patients.
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8: What did we learn? Most drugs tested in lab models of DIPG will not work, and most will fail in vivo because the blood brain barrier is so tight. Rigorous lab testing is essential to ensure that only drugs with real potential are taken to clinical trial.
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7: Examining the mechanism of action identified fenretinide acting via "old" and "new" pathways: inhibition of PDGFR; upregulation of ER stress and UPR; downregulation of neurogenesis; induction of mitophagy and autophagy.
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6: Of the 3,500 drugs screened - fenretinide was the only one to be active in vitro, to penetrate the blood brain barrier, and to show activity in DIPG mouse models.
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5: We then tested all 6 drugs in mouse models of DIPG - and all but one failed! Most of them showed no activity at all - the reason: for all but one, they did not penetrate the blood brain barrier and therefore were inactive against the tumour.
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4: Extensive review suggested only 28 of these compounds were likely to cross the blood brain barrier - which we know is intact in DIPG. Further testing against more cells, and normal cell cultures whittled this group down to only 6 drugs that were likely to be active.
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3: Despite including hundreds of anti-cancer drugs, most of them were completely inactive against DIPG cells - however a small number - 90 - were highly potent.
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2: We started this project by doing a high throughput drug screen against multiple DIPG cell cultures - one of the largest screens ever undertaken - using thousands of drugs.
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Great to be able to share our latest manuscript - results of many many years of work from our lab and collaborators: High-throughput in vitro drug screening and in vivo studies identify fenretinide as a brain-penetrant DMG therapeutic. See 🧵for details:
academic.oup.com
AbstractBackground. Diffuse midline glioma, characterized by H3K27 alteration (DMG), is the predominant high-grade glioma in children. It commonly originat
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RT @ISPNO2026: Welcome to 2025 - ISPNO in Sydney Australia is now coming up next year! Start getting ready!.
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