A5034602185- Glioma Diagnosis and Treatment
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Telomeres, Telomerase, and Senescence
- Advanced Neural Network Applications
- Circular RNAs in diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Ferroptosis and cancer prognosis
- Mitochondrial Function and Pathology
- Cytokine Signaling Pathways and Interactions
- Microtubule and mitosis dynamics
- Neuroblastoma Research and Treatments
- Ubiquitin and proteasome pathways
- Ocular Oncology and Treatments
- Histone Deacetylase Inhibitors Research
- Immune cells in cancer
- Adrenal and Paraganglionic Tumors
- Melanoma and MAPK Pathways
- Radiomics and Machine Learning in Medical Imaging
- Pharmaceutical studies and practices
- Neurogenesis and neuroplasticity mechanisms
- interferon and immune responses
- Cancer therapeutics and mechanisms
- Caveolin-1 and cellular processes
- Domain Adaptation and Few-Shot Learning
Hopp Children's Cancer Center Heidelberg
2022-2024
Heidelberg University
2021-2024
German Cancer Research Center
2021-2024
National Center for Tumor Diseases
2024
University Hospital Heidelberg
2024
CRUK Lung Cancer Centre of Excellence
2021-2022
University College London
2020-2022
Abstract Glioblastomas are hierarchically organised tumours driven by glioma stem cells that retain partial differentiation potential. Glioma maintained in specialised microenvironments, but whether, or how, they undergo lineage progression outside of these niches remains unclear. Here we identify the white matter as a differentiative niche for glioblastomas with oligodendrocyte competency. Tumour contact acquire pre-oligodendrocyte fate, resulting decreased proliferation and invasion....
Abstract Pediatric low-grade gliomas (pLGG) show heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. Thus, more complex stratification biomarkers are needed identify patients likely benefit from MAPKi therapy. Here, we MAPK-related genes enriched MAPKi-sensitive cell lines using the GDSC dataset and apply them calculate class-specific sensitivity scores (MSSs) via single-sample gene set enrichment analysis. The MSSs discriminate non-sensitive cells significantly correlate...
Abstract Introduction Patients with pediatric low-grade gliomas (pLGGs), the most common primary brain tumors in children, can often benefit from MAPK inhibitor (MAPKi) treatment. However, rapid tumor regrowth, also referred to as rebound growth, may occur once treatment is stopped, constituting a significant clinical challenge. Methods Four patient-derived glioma models were investigated model growth vitro based on viable cell counts response MAPKi and withdrawal. A multi-omics dataset (RNA...
Abstract Purpose Although pediatric low-grade gliomas (pLGG) are the most common brain tumors, patient-derived cell lines reflecting pLGG biology in culture scarce. This also applies to subtype pilocytic astrocytoma (PA). Conventional approaches adapted from higher-grade tumors fail PA due oncogene-induced senescence (OIS) driving tumor cells into arrest. Here, we describe a modeling workflow using Simian Virus large T antigen (SV40-TAg) circumvent OIS. Methods 18 tissue samples (17 (94%)...
Abstract Pilocytic astrocytomas (PA), the most common pediatric brain tumors, exhibit MAPK pathway alterations leading to its constitutive activation. They are also associated with low proliferation index due oncogene-induced senescence (OIS), sustained by senescence-associated secretory phenotype (SASP) factors. Little is known about downstream consequences of activation OIS-SASP, and molecular implications inhibition in senescent PA cells. Senescent DKFZ-BT66 cells derived from a primary...
Abstract Patients with pediatric low-grade gliomas (pLGG), the most common primary brain tumor in children, can often benefit from MAPK inhibitor (MAPKi) treatment. However, rapid regrowth, also referred to as rebound growth, may occur once treatment is stopped, constituting a significant clinical challenge. Four patient-derived pLGG models were investigated model growth vitro based on viable cell counts response MAPKi and withdrawal. A multi-omics dataset of encompassing different...
Abstract Pediatric low-grade gliomas, a diverse group of WHO grade 1 and 2 glial or glioneural tumors, comprise the most common category primary brain tumors in children. The majority these are driven by alterations MAPK pathway, making them principle susceptible to MAPKi therapy. While patients often benefit from during treatment, tumor rebound may occur once treatment is stopped, constituting significant clinical challenge. BT-40, patient-derived cells with molecular features pleomorphic...
Abstract INTRODUCTION Pilocytic astrocytomas (PA) are the most common pediatric brain tumors. They characterized by MAPK pathway alterations, leading to its constitutive activation and modulating balance between proliferation oncogene-induced senescence (OIS) sustained senescence-associated secretory phenotype (SASP). Little is known about molecular implications of inhibition in proliferating senescent tumor compartments. METHODS DKFZ-BT66 cells derived from a primary KIAA:BRAF-fusion...
Summary Glioblastomas are hierarchically organised tumours driven by glioma stem cells that retain partial differentiation potential. Glioma maintained in specialised microenvironments, but how they undergo lineage progression outside of these niches remains unclear. Here we identify the white matter as a differentiative niche for glioblastomas with oligodendrocyte competency. Tumour contact acquire pre-oligodendrocyte-like fate, resulting decreased proliferation and invasion....
Abstract Pilocytic astrocytomas (PA) are the most common pediatric brain tumors. They characterized by driving alterations in mitogen-activated protein kinase (MAPK) pathway, leading to its constitutive activation and modulating balance between cell proliferation oncogene-induced senescence (OIS) sustained senescence-associated secretory phenotype (SASP) factors. This makes PA susceptible MAPK inhibitor (MAPKi) therapies, which show encouraging results phase 1/2 clinical trials. However,...
Abstract Pediatric low-grade glioma (pLGG), the most common brain tumors in children, are driven by alterations MAPK pathway. Several clinical trials have shown potential for inhibitor (MAPKi) treatment pLGG. However, range of response to MAPKi is heterogeneous, even between sharing same driving alteration. A predictive stratification tool needed identify that will be sensitive inhibition. We generated sensitivity gene signatures each class (BRAFi, MEKi, ERKi), based on MAPK-related genes...
Abstract Introduction Pilocytic astrocytomas (PA) are the most common pediatric brain tumors. They characterized by MAPK pathway alterations, leading to its constitutive activation and modulating balance between cell proliferation oncogene-induced senescence (OIS) sustained senescence-associated secretory phenotype (SASP) factors. This makes PA suitable for inhibitor (MAPKi) therapies, showing encouraging results in phase 1/2 clinical trials. Little is known about molecular implications of...