David D. Eisenstat
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View article: EXTH-75. Precision Immunotherapy for Paediatric High-Grade Glioma: PDGFRα CAR T Cells Show Potent Activity in a Rare Patient-Derived Model
EXTH-75. Precision Immunotherapy for Paediatric High-Grade Glioma: PDGFRα CAR T Cells Show Potent Activity in a Rare Patient-Derived Model Open
Paediatric high-grade gliomas (pHGG) remain among the most lethal childhood cancers, and the subset of H3K27M-wild-type diffuse gliomas is especially under-studied due to a lack of representative models. Here, we describe a rare, clinicall…
View article: The DLX/Notch axis is necessary for spatiotemporal regulation of neural cell fate
The DLX/Notch axis is necessary for spatiotemporal regulation of neural cell fate Open
The neuronal-glial cell fate switch during forebrain development is highly regulated. DLX transcription factors are necessary for promoting GABAergic interneuron differentiation and migration but the mechanisms for concomitant repression o…
View article: Application of spatial transcriptomics across organoids: a high-resolution spatial whole-transcriptome benchmarking dataset
Application of spatial transcriptomics across organoids: a high-resolution spatial whole-transcriptome benchmarking dataset Open
Summary Stem cell-derived organoid models hold great promise to model tissue-specific disease. To enable this, it is crucial to determine how their composition compares to endogenous organs. However, technologies such as spatial transcript…
View article: Deciphering UBE4B phosphorylation dynamics: a key mechanism in p53 accumulation and cancer cell response to DNA damage
Deciphering UBE4B phosphorylation dynamics: a key mechanism in p53 accumulation and cancer cell response to DNA damage Open
The p53 tumor suppressor protein plays a crucial role in detecting and eliminating various oncogenic threats by promoting processes such as cell cycle arrest, DNA repair, senescence, and apoptosis. UBE4B is essential for negatively regulat…
View article: Multidimensional, integrative profiling identifies BCL2L1 methylation as a predictor of MCL1 dependency in pediatric malignancies
Multidimensional, integrative profiling identifies BCL2L1 methylation as a predictor of MCL1 dependency in pediatric malignancies Open
Pediatric high-grade gliomas (pHGGs) are the most aggressive brain tumors in children, necessitating innovative therapies to improve outcomes. Unlike adult gliomas, recent research reveals that childhood gliomas have distinct biological fe…
View article: IDH-mutant gliomas in children and adolescents - from biology to clinical trials
IDH-mutant gliomas in children and adolescents - from biology to clinical trials Open
Gliomas account for nearly 30% of all primary central nervous system (CNS) tumors in children and adolescents and young adults (AYA), contributing to significant morbidity and mortality. The updated molecular classification of gliomas defi…
View article: The ParClusterers Benchmark Suite (PCBS): A Fine-Grained Analysis of Scalable Graph Clustering
The ParClusterers Benchmark Suite (PCBS): A Fine-Grained Analysis of Scalable Graph Clustering Open
We introduce the ParClusterers Benchmark Suite (PCBS) -- a collection of highly scalable parallel graph clustering algorithms and benchmarking tools that streamline comparing different graph clustering algorithms and implementations. The b…
View article: CNSC-36. REGULATION OF CELL FATE IN PAEDIATRIC HIGH-GRADE GLIOMA BY THE HOMEOBOX TRANSCRIPTION FACTOR DLX2
CNSC-36. REGULATION OF CELL FATE IN PAEDIATRIC HIGH-GRADE GLIOMA BY THE HOMEOBOX TRANSCRIPTION FACTOR DLX2 Open
Paediatric high-grade gliomas (pHGG) are nearly uniformly fatal cancers that arise predominantly in children and adolescents and encompass Diffuse Midline Glioma (DMG) and Diffuse Hemispheric Glioma (DHG). Most patients harbour mutations i…
View article: Active Beta-Catenin (ABC) promotes an invasive phenotype in pediatric osteosarcoma
Active Beta-Catenin (ABC) promotes an invasive phenotype in pediatric osteosarcoma Open
Osteosarcoma (OS) is an aggressive primary bone malignancy with peak incidence in children and adolescents. Despite current multimodal treatments, there has been little change in overall survival outcomes in the last two decades. The canon…
View article: Supplementary Data from ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma
Supplementary Data from ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma Open
All Supplementary Tables
View article: Data from ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma
Data from ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma Open
Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is…
View article: Supplementary Data from ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma
Supplementary Data from ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma Open
All Supplementary Figures and their captions.
View article: Supplementary Data from ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma
Supplementary Data from ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma Open
All Supplementary Tables
View article: Supplementary Data from ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma
Supplementary Data from ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma Open
All Supplementary Figures and their captions.
View article: GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant
GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant Open
Diffuse hemispheric gliomas, H3G34R/V-mutant (DHG-H3G34), are lethal brain tumors lacking targeted therapies. They originate from interneuronal precursors; however, leveraging this origin for therapeutic insights remains unexplored. Here, …
View article: CNSC-03. LINKING CELL FATE DETERMINATION IN THE EMBRYONIC FOREBRAIN TO PEDIATRIC HIGH-GRADE GLIOMA
CNSC-03. LINKING CELL FATE DETERMINATION IN THE EMBRYONIC FOREBRAIN TO PEDIATRIC HIGH-GRADE GLIOMA Open
BACKGROUND Pediatric high-grade gliomas are treatment resistant, usually fatal cancers encompassing diffuse midline glioma, K27-altered (DMG), and diffuse hemispheric glioma, G34R/V (DHG). Most patients harbour canonical and non-canonical …
View article: DIPG-54. PREDICTING EARLY DEATH IN DIFFUSE MIDLINE GLIOMA
DIPG-54. PREDICTING EARLY DEATH IN DIFFUSE MIDLINE GLIOMA Open
BACKGROUND Diffuse midline glioma (DMG) is an invariably fatal diagnosis with a median survival of 9-11 months. While early death is uncommon, such cases do exist. Identification of children at risk of short-term survival can support clini…
View article: LGG-12. INTEGRATED CLINICAL AND MOLECULAR CHARACTERIZATION OF 200 DISSEMINATED PEDIATRIC LOW-GRADE GLIOMAS
LGG-12. INTEGRATED CLINICAL AND MOLECULAR CHARACTERIZATION OF 200 DISSEMINATED PEDIATRIC LOW-GRADE GLIOMAS Open
Pediatric low-grade gliomas (PLGG) have excellent outcomes overall but are a major clinical challenge when disseminated. Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a recognised entity both clinically and pathologically, however m…
View article: MDB-90. PRIMARY LEPTOMENINGEAL MEDULLOBLASTOMA: A SINGLE-SITE RETROSPECTIVE STUDY OF 5 CASES
MDB-90. PRIMARY LEPTOMENINGEAL MEDULLOBLASTOMA: A SINGLE-SITE RETROSPECTIVE STUDY OF 5 CASES Open
BACKGROUND Primary leptomeningeal medulloblastoma without mass is a rare entity with fewer than 10 reported paediatric cases. Establishing an accurate diagnosis is challenging and reported outcomes are very poor. METHODS We conducted a ret…
View article: The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models
The Landscape of Pediatric High-Grade Gliomas: The Virtues and Pitfalls of Pre-Clinical Models Open
Pediatric high-grade gliomas (pHGG) are malignant and usually fatal central nervous system (CNS) WHO Grade 4 tumors. The majority of pHGG consist of diffuse midline gliomas (DMG), H3.3 or H3.1 K27 altered, or diffuse hemispheric gliomas (D…
View article: Precision-guided treatment in high-risk pediatric cancers
Precision-guided treatment in high-risk pediatric cancers Open
Recent research showed that precision medicine can identify new treatment strategies for patients with childhood cancers. However, it is unclear which patients will benefit most from precision-guided treatment (PGT). Here we report consecu…
View article: Management of patients with diffuse intrinsic pontine glioma in Australia and New Zealand: Australian and New Zealand Children's Haematology/Oncology Group position statement
Management of patients with diffuse intrinsic pontine glioma in Australia and New Zealand: Australian and New Zealand Children's Haematology/Oncology Group position statement Open
Introduction The main mission of the Australian and New Zealand Children's Haematology and Oncology Group (ANZCHOG) is to develop and facilitate local access to the world's leading evidence‐based clinical trials for all paediatric cancers,…
View article: PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma
PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma Open
Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR/Cas9 loss-of-function gene deletion scre…
View article: A paradigm shift in how we treat pediatric low-grade glioma—Targeting the molecular drivers
A paradigm shift in how we treat pediatric low-grade glioma—Targeting the molecular drivers Open
Journal Article Corrected proof A paradigm shift in how we treat pediatric low-grade glioma—Targeting the molecular drivers Get access David S Ziegler, David S Ziegler Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, …
View article: Lessons learnt in the first year of an Australian pediatric cardio oncology clinic
Lessons learnt in the first year of an Australian pediatric cardio oncology clinic Open
Background Modern oncological therapies together with chemotherapy and radiotherapy have broadened the agents that can cause cardiac sequelae, which can manifest for pediatric oncology patients while on active treatment. Recommendations fo…
View article: EXTH-31. EXPLOITING THE GENETIC DEPENDENCY ON PI3K/MTOR SIGNALING FOR THE TREATMENT OF H3-ALTERED DIFFUSE MIDLINE GLIOMA
EXTH-31. EXPLOITING THE GENETIC DEPENDENCY ON PI3K/MTOR SIGNALING FOR THE TREATMENT OF H3-ALTERED DIFFUSE MIDLINE GLIOMA Open
Recurring activating mutations, amplifications and allelic loss of the negative repressors of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling genes are overarching contributors to the poor survival of patients with H3K2…
View article: EXTH-36. COMBINING ONC201 AND PAXALISIB FOR THE TREATMENT OF DIFFUSE MIDLINE GLIOMA (DMG); THE PRECLINICAL RESULTS UNDERPINNING THE INTERNATIONAL PHASE II CLINICAL TRIAL (NCT05009992)
EXTH-36. COMBINING ONC201 AND PAXALISIB FOR THE TREATMENT OF DIFFUSE MIDLINE GLIOMA (DMG); THE PRECLINICAL RESULTS UNDERPINNING THE INTERNATIONAL PHASE II CLINICAL TRIAL (NCT05009992) Open
Diffuse midline gliomas (DMGs) diagnosed in the pons (DIPG) are universally fatal central nervous system tumors and are the leading cause of cancer-related death in children. Palliative radiotherapy is the only recognized treatment, with m…
View article: MODL-12. REGULATION OF OLIGODENDROGLIAL PROGENITOR CELL (OPC) CELL FATE IN DIFFUSE MIDLINE GLIOMA (DMG) BY THE HOMEOBOX TRANSCRIPTION FACTOR DLX2
MODL-12. REGULATION OF OLIGODENDROGLIAL PROGENITOR CELL (OPC) CELL FATE IN DIFFUSE MIDLINE GLIOMA (DMG) BY THE HOMEOBOX TRANSCRIPTION FACTOR DLX2 Open
Diffuse midline glioma, K27-altered (DMG) is a treatment resistant, uniformly fatal cancer that arises predominantly in children. 80% of patients with DMG harbor K27M mutations in canonical histone variants H3.3 and H3.1, leading to global…
View article: Precision-guided treatment improves outcomes for children with high-risk cancers
Precision-guided treatment improves outcomes for children with high-risk cancers Open
Recent reports have shown that precision medicine can identify new treatment strategies for childhood cancer patients. However, it remains unclear which patients will benefit most from precision-guided treatment (PGT). Here we report 384 c…