2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
June 6th, 2025
Version: 3
Queen Mary University of London
cancer biology
biorxiv

Modelling medulloblastoma pathogenesis and treatment in human cerebellar organoids.

Willott, T. O.Open in Google Scholar•Nicholson, J. G.Open in Google Scholar•Xiao, Y.Open in Google Scholar•Ogunbiyi, O. K.Open in Google Scholar•Draper, B.Open in Google Scholar•Mistry, T.Open in Google Scholar•Donovan, L.Open in Google Scholar•Zabet, N. R.Open in Google Scholar•Merve, A.Open in Google Scholar•Badodi, S.Open in Google Scholaret al.

Faithful genetically engineered in vivo models of medulloblastoma (MB) are currently available only for some molecular subgroups, in keeping with recent studies showing the unique role of human-specific progenitors in the development of G3 and G4 MB subgroups. We generated human cerebellar organoids (CbO) from expanded potential stem cells (EPSC) and characterised their epigenetic and transcriptomic profile compared to the developing human cerebellum. We show the presence of sub compartment-specific cerebellar lineages linked to MB formation, including populations expressing signature genes of putative G3 and G4 MB cells-of-origin. We show that these lineages can be genetically engineered to model MB tumour onset. Moreover, we demonstrate that CbO sustain proliferation and invasion of G3/4 MB cells in a 3D co-culture model (CbO-MB) while preserving their molecular identity, and that treatment of CbO-MB with anti-tumour compounds recapitulate the efficacy of in vivo drug testing in xenograft models

Similar Papers

biorxiv
Sat Jun 07 2025
Targeting Neutrophil Extracellular Traps to inhibit Colon Cancer Tumor Necrosis and Metastasis
Necrosis, conventionally thought of as a passive consequence of aggressive tumor growth, is associated with poor prognosis in colorectal cancer (CRC). We recently discovered that necrosis can be caused by neutrophil extracellular trap (NET) aggregates driving vascular occlusion within the tumor vasculature in models of breast cancer. Here, we evaluated the role of NETs in inducing necrosis and met...
Gazzara, E.
•
Adrover, J. M.
•
Lui, A.
•
Han, S.
...•
Gholami, S.
biorxiv
Fri Jun 06 2025
Statin-dye conjugates for selective targeting of KRAS mutant cancer cells
Over 90% of pancreatic ductal adenocarcinoma (PDAC) patients involve KRAS mutations (KRASMUT), for which current treatment options are limited. Statins, commonly used to lower cholesterol, have demonstrated certain selective toxicity towards KRAS-transformed cells, prompting the question of whether statins could achieve selective uptake specifically in KRASMUT cells. To investigate this, we synthe...
Moon, H.-r.
•
Cai, Z.
•
Cho, B. K.
•
Chang, H.
...•
Ryu, J. H.
biorxiv
Fri Jun 06 2025
Increasing Stemness Drives Prostate Cancer Progression, Plasticity, Therapy Resistance and Poor Patient Survival
Cancer progression involves loss of differentiation and acquisition of stem cell-like traits, broadly referred to as "stemness". Here, we test whether the level of stemness, assessed by a transcriptome-derived Stemness score, can quantitatively track prostate cancer (PCa) development, progression, therapy resistance, metastasis, plasticity, and patient survival. Integrative analysis of transcripto...
Liu, X.
•
Cortes, E.
•
Ji, Y.
•
Zhao, K.
...•
Tang, D. G.
biorxiv
Fri Jun 06 2025
BEHAV3D Tumor Profiler to map heterogeneous cancer cell behavior in the tumor microenvironment
Intravital microscopy (IVM) enables live imaging of animals at single-cell level, offering essential insights into cancer progression. This technique allows for the observation of single-cell behaviors within their natural 3D tissue environments, shedding light on how genetic and microenvironmental changes influence the complex dynamics of tumors. IVM generates highly complex datasets that often e...
Rios-Jimenez, E.
•
Zomer, A.
•
Collot, R.
•
Barrera Roman, M.
...•
Alieva, M.
biorxiv
Fri Jun 06 2025
Astrocyte reprogramming drives tumor progression and chemotherapy resistance in agent-based models of breast cancer brain metastases
Breast cancer brain metastases (BCBM) affect nearly 90,000 patients annually in the United States and carry a significant risk of mortality. As metastatic lesions develop, the unique milieu of the brain microenvironment shapes disease progression and therapeutic response. Among resident brain cells, astrocytes are both the most common, and are increasingly recognized as key regulators of this proc...
Kaur, R.
•
Barker-Clarke, R.
•
Dhawan, A.
biorxiv
Fri Jun 06 2025
Sequential Activation of Senescence and Apoptosis by ONG41008 Eliminated the Human Pancreatic Ductile Adenocarcinoma in nude mice and xenografted human lung cancer
Current therapeutic limitations associated with pancreatic ductal adenocarcinoma (PDAC) are still evident. We have found that ONG41008, the first human synthetic polyphenol, is able to eradicate PDAC in a nude mouse model. ONG41008 is known to potently attenuate human TGF-{beta} production, inducing both anti-fibrotic capacity and anticancer potential through senescence-coupled apoptosis (SCA). Th...
Youn, B.-S.
•
Kim, K.
•
Kim, Y.
biorxiv
Fri Jun 06 2025
Lactate cannot replace glucose for maintaining the viability of mouse and human glioma cells
Objectives: Aerobic lactic acid fermentation (the \'\'Warburg effect\'\') is associated with OxPhos insufficiency and altered energy metabolism in most cancers. Whether lactate is a major fuel in cancer cells remains debated. This study investigated whether lactate could serve as a metabolic fuel in glioma cells and replace glucose to support viability. Methods: A bioluminescence ATP assay and cal...
Miller, E. Y.
•
Duraj, T.
•
Ta, N. L.
•
Lee, D. C.
...•
Seyfried, T. N.
biorxiv
Thu Jun 05 2025
Contrastive Learning-Enhanced Drug Metabolite Prediction Drives the Discovery of an Orally Bioavailable RSK4 Inhibitor for Esophageal Cancer
Drug metabolism liabilities are a major bottleneck in drug development, necessitating accurate metabolite prediction tools. While AI-driven methods have advanced, challenges remain in achieving high-precision, robustness, broad reaction coverage and seamless integration into the drug development workflow. To address this, we first constructed the most comprehensive human-specific drug metabolism d...
He, H.
•
Zhang, M.
•
Yang, X.
•
He, S.
...•
Li, S.
biorxiv
Thu Jun 05 2025
Leveraging autophagy and pyrimidine metabolism to target pancreatic cancer
Autophagy inhibitors are promising compounds to treat pancreatic ductal adenocarcinoma (PDA) but their efficacy in patients is unclear, highlighting a need to understand mechanisms of resistance. We used a novel approach to uncover metabolic adaptations that bypass autophagy inhibition. Utilizing PDA cells with acquired resistance to different autophagy inhibitors, we found that severe autophagy d...
Dufresne, S.
•
Kuna, R. S.
•
Wong, K.
•
Komarla, A.
...•
Towers, C. G.