OSCR

Brain assembloids reveal efficacy and off target effects in high grade glioma brain cancer.

Overview

Authors: Farhana Amy Sarker1,2, Yuyan Chen1,2, Victoria Prior1,2, Sam Bax1,2, Louise Orcheston-Findlay2, Tom Grundy1,2,3, Thuvarahan Jegathees1,2, Robert Utama3, Martin Engel3, Tristan Rawling4, Yassir Al Zubaidi5, Michael Murray5, Geraldine Margaret O’Neill1,2
ORCID iDs: Yuyan Chen, Victoria Prior, Tom Grundy, Thuvarahan Jegathees, Martin Engel, Tristan Rawling, Michael Murray, Geraldine Margaret O’Neill
  1. Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia
  2. Children’s Cancer Research Unit, The Children’s Hospital at Westmead, Sydney, NSW 2145, Australia
  3. Inventia Life Science Pty Ltd., Sydney, NSW, Australia
  4. School of Mathematical and Physical Sciences, University of Technology, Sydney, NSW 2015, Australia
  5. Pharmacogenomics and Drug Development Group, Discipline of Pharmacology, School of Medical Sciences, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia
Institutions: The University of Sydney (Australia); Children's Hospital at Westmead (Australia); Westmead Hospital (Australia); University of Technology Sydney (Australia)
Journal: iScience, volume 29, issue 9, article 117247
Dates: received 20 August 2025; accepted 3 August 2026; published online 19 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.isci.2026.117247 · PMID 42662550 · PMCID PMC13521100 · OpenAlex W7203732262
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: other condition (population), clinical / translational (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Evoked potentials, fMRI & imaging
Keywords: high grade glioma, anti-invasive therapy, organoid co-cultures, side effects
Topic: Glioma Diagnosis and Treatment (Genetics, Medicine), according to OpenAlex
Funding: The Kids' Cancer Project; University of Sydney; University of Sydney School of Medicine
Citations: not cited yet (Europe PMC); 42 references in the paper
Research resources: RRID:AB_10622000, MET (D1C2) Rabbit Monoclonal Antibody RRID:AB_10858224, RRID:AB_10972486, RRID:AB_2080597, Dvl2 (30D2) Rabbit Monoclonal Antibody RRID:AB_2093336, RRID:AB_2340607, RRID:AB_2534697, RRID:AB_2536381, RRID:AB_2556542, RRID:AB_2556546, RRID:AB_2763448, RRID:AB_2799282, RRID:AB_330744, RRID:AB_331646, RRID:AB_647130, RRID:AB_92642, U87MG RRID:CVCL_0022, HEK293T RRID:CVCL_1926, RRID:CVCL_9773, SU-DIPG-XXIV (DIPG24) RRID:CVCL_C1MY, WK1 RRID:CVCL_VS54

Abstract

Anti-invasive therapies may limit damage to healthy brain tissue caused by invading high-grade glioma (HGG) cells. However, the actin machinery that drives invasion is shared by cancer and normal cells, and therefore, there is a risk of on-target, off-tumor side effects. We compared omega 3 polyunsaturated fatty acid epoxide analog p-tolyl-ureidopalmitic acid (PTU) effects between HGG multicellular tumor spheroids (MCTSs) embedded in Matrigel and assembloids consisting of HGG MCTS with embryonic stem cell-derived cortical brain organoids. PTU inhibited cofilin and induced cell rounding consistent with a loss of filamentous (F-) actin and efficiently inhibited invasion in 3D Matrigel invasion assays, but effects were cell line specific in assembloids. Immunofluorescence and GeoMx Digital Spatial Profiling of assembloids revealed that PTU disrupts signaling in cancer cells and the “healthy” cortical organoid. This study demonstrates a methodological approach for in vitro testing of efficacy and safety for anti-invasive therapies for HGG.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

Datasets cited

Data and code availability

No high-throughput sequencing data were generated in this study. All data supporting the findings of this study are available from the corresponding author upon reasonable request.

Original western blot images have been deposited at Mendeley at https://doi.org/10.17632/7tb99r5f65.1 and are publicly available. Microscopy data reported in this study will be shared by the lead contact upon request.

This study does not report original code

Any additional information required to reanalyze the reported data is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Authors: added Yuyan Chen (0000-0002-2894-1430); Victoria Prior (0000-0002-2285-5398); Tom Grundy (0009-0000-1550-4234); Thuvarahan Jegathees (0000-0001-6478-3946); Martin Engel (0000-0001-7602-1340); Michael Murray (0000-0002-4233-7619); Geraldine Margaret O’Neill (0000-0001-9997-8794); removed Yuyan Chen; Victoria Prior; Tom Grundy; Thuvarahan Jegathees; Martin Engel; Michael Murray; Geraldine Margaret O’Neill

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 13 authors, 4 keywords, 3 funders, 42 references, 21 RRIDs.

Cite

This paper

Sarker, F. A., Chen, Y., Prior, V., Bax, S., Orcheston-Findlay, L., Grundy, T., Jegathees, T., Utama, R., Engel, M., Rawling, T., Al Zubaidi, Y., Murray, M., & O’Neill, G. M. (2026). Brain assembloids reveal efficacy and off target effects in high grade glioma brain cancer. iScience, 29(9), 117247. https://doi.org/10.1016/j.isci.2026.117247

BibTeX

@article{sarker2026brain,
author = {Sarker, Farhana Amy and Chen, Yuyan and Prior, Victoria and Bax, Sam and Orcheston-Findlay, Louise and Grundy, Tom and Jegathees, Thuvarahan and Utama, Robert and Engel, Martin and Rawling, Tristan and Al Zubaidi, Yassir and Murray, Michael and O’Neill, Geraldine Margaret},
title = {{Brain assembloids reveal efficacy and off target effects in high grade glioma brain cancer}},
journal = {iScience},
year = {2026},
month = aug,
volume = {29},
number = {9},
pages = {117247},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.117247},
url = {https://doi.org/10.1016/j.isci.2026.117247},
pmid = {42662550},
pmcid = {PMC13521100}
}

RIS

TY - JOUR
AU - Sarker, Farhana Amy
AU - Chen, Yuyan
AU - Prior, Victoria
AU - Bax, Sam
AU - Orcheston-Findlay, Louise
AU - Grundy, Tom
AU - Jegathees, Thuvarahan
AU - Utama, Robert
AU - Engel, Martin
AU - Rawling, Tristan
AU - Al Zubaidi, Yassir
AU - Murray, Michael
AU - O’Neill, Geraldine Margaret
TI - Brain assembloids reveal efficacy and off target effects in high grade glioma brain cancer
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/08/19
VL - 29
IS - 9
SP - 117247
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.117247
UR - https://doi.org/10.1016/j.isci.2026.117247
LA - en
ER -

CSL-JSON

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