109 Multi-omic integration reveals intra-tumour heterogeneity and identifies disulfiram and copper as a synergistic therapy in paediatric ependymoma
Clicks: 3
ID: 326824
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Emerging Content
0.6
/100
3 views
2 readers
AI Quality Assessment
Not analyzed
Readership in this journal
EmergingRanked #212 of 219 articles by views in journal of neuro-oncology
Most read
Least read
Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 219 in total.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Abstract Introduction Ependymoma (EPN) is the second most malignant paediatric brain tumour. The PF-A subgroup, associated with a hypoxic microenvironment, has a dismal survival rate of 50%, with clinical trials failing to demonstrate a significant survival advantage from chemotherapy to date. We present a multi-omic integration investigating whether spatially-distinct tumour microenvironments represent targetable metabolic niches in PF-A EPN. Methods Surgical sampling of spatially-distinct regions from eight PF-A patients was performed, with metabolites and RNA simultaneously extracted and analysed using LC-MS and RNA-seq. Integration of metabolites and RNA was performed using Metscape3 with functional assays evaluating proliferation and invasion in 2D and 3D patient-derived in-vitro cell models. LC-MS and qPCR were used to analyse post-treatment changes of our lead drug combination under hypoxia and normoxia. Clonogenic assays investigated radiosensitisation (±2 Gy) and in-vivo tolerability was evaluated in non-tumour-bearing mice (DSF/Cu2+ 200/4 mg/kg, i.p.). Results Multi-omic integration identified 124 dysregulated metabolic pathways, demonstrating heterogeneity within and across PF-A tumours. Based on the identified metabolically relevant genes, Disulfiram (Dsf) and Cu2+ were highlighted as potential therapeutic agents showing impaired metabolic viability and invasion in 2D and 3D models of PF-A EPN, with radiosensitising effects in 2D clonogenic assays and limited chemosensitivity observed in human cerebellar astrocytes. LC-MS revealed Dsf/Cu2+ disrupts mitochondrial fatty acid oxidation (normoxia) and TCA cycle intermediates (hypoxia). In vivo, DSF/Cu2+ showed no weight loss or overt toxicity in non-tumour-bearing mice. This combination also demonstrated efficacy in additional paediatric in-vitro models, suggesting pan-cancer potential. Conclusions This is the first instance where multi-omic data integration and intra-tumor heterogeneity have been investigated for paediatric EPN, revealing novel therapeutic targets in the context of gene-metabolite correlations.
| Reference Key |
openalex_W7204488094
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Alina Pandele, Alison Whitby, Sandra Martínez‐Jarquín, Chiara Bastiancich, Donald Macarthur, Ian Kamaly-Asl, David Barrett, Richard Grundy, Dong-Hyun Kim, Ruman Rahman |
| Journal | journal of neuro-oncology |
| Year | 2026 |
| DOI |
10.1093/neuonc/noag172.005
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.