High-throughput 3D engineered paediatric tumour models for precision medicine
Precision medicine for paediatric and adult cancers that incorporates drug sensitivity profiling can identify effective therapies for individual patients. However, obtaining adequate biopsy samples for high-throughput (HTP) screening remains challenging, with tumours needing to be expanded in culture or patient-derived xenografts, this is time-consuming and often unsuccessful. Herein, we have developed paediatric patient-derived tumour models using an engineered extracellular matrix (ECM) tissue mimic hydrogel system and HTP 3D bioprinting. Gene expression analysis from a neuroblastoma and sarcoma paediatric patient cohort identified key components of the ECM in these tumour types. Engineered hydrogels with ECM-mimic peptides were used to bioprint and create patient-specific tumouroids using patient-derived cells from xenograft models, and the approach was further confirmed on direct patient tumour samples. Bioprinted tumouroids from the PDX models recapitulated the genetic and phenotypic characteristics of the original tumours and retained tumourigenicity. HTP drug screening of these models identified individualised drug sensitivities. Our approach offers a timely and clinically relevant technology platform for precision medicine in paediatric cancers, potentially transforming preclinical testing across multiple cancer types.
Authors
- Kathleen Kimpton (ORCID: https://orcid.org/0000-0002-9752-7022)
- Joanna N. Skhinas (ORCID: https://orcid.org/0000-0001-8797-8228)
- Emmy D.G. Fleuren (ORCID: https://orcid.org/0000-0001-6202-6861)
- Angela Lin
- Alvin Kamili (ORCID: https://orcid.org/0000-0002-4864-1195)
- Gábor Tax (ORCID: https://orcid.org/0000-0003-4530-0798)
- Philipp Graber (ORCID: https://orcid.org/0000-0002-3157-1434)
- Maria Kavallaris (ORCID: https://orcid.org/0000-0003-2309-898X)
- Jinhan Xie (ORCID: https://orcid.org/0000-0001-8771-9533)
- M. Emmy M. Dolman (ORCID: https://orcid.org/0000-0002-0567-5918)
- MoonSun Jung (ORCID: https://orcid.org/0000-0003-0548-0683)
- Marie Wong (ORCID: https://orcid.org/0000-0003-0066-6606)
- J. Justin Gooding (ORCID: https://orcid.org/0000-0002-5398-0597)
- John P. Grady (ORCID: https://orcid.org/0000-0001-9667-3872)
- Chelsea Mayoh (ORCID: https://orcid.org/0000-0002-6398-3046)
- Andrew J. Gifford (ORCID: https://orcid.org/0000-0002-4092-2347)
- Loretta M. S. Lau (ORCID: https://orcid.org/0000-0002-3172-0970)
- David M. Thomas (ORCID: https://orcid.org/0000-0002-2527-5428)
- Ashleigh M. Fordham (ORCID: https://orcid.org/0000-0003-4667-6244)
- Pooja Venkat (ORCID: https://orcid.org/0000-0002-9171-7562)
- Mark J. Cowley (ORCID: https://orcid.org/0000-0002-9519-5714)
- Lujing Cui (ORCID: https://orcid.org/0000-0003-4762-3099)
- Jie Mao (ORCID: https://orcid.org/0009-0009-6428-7788)
- Sarah Ghamrawi (ORCID: https://orcid.org/0000-0002-5456-1220)
- Nicole Graf (ORCID: https://orcid.org/0000-0003-3608-2071)
- Jamie I. Fletcher (ORCID: https://orcid.org/0000-0003-2949-9469)
- Eric Y. Du (ORCID: https://orcid.org/0000-0002-1884-7299)
- Zara Barger
- Valentina Poltavets
Institutions
- The University of Sydney (AU)
- New South Wales Department of Health (AU)
- Garvan Institute of Medical Research (AU)
- Cancer Institute of New South Wales (AU)
- Children's Hospital at Westmead (AU)
- Westmead Hospital (AU)
- UNSW Sydney (AU)
- Prince of Wales Hospital (AU)
- Children's Cancer Institute Australia (AU)
- Melanoma Institute Australia (AU)
- St Vincent's Clinic (AU)
- Sydney Children's Hospital (AU)
- Princess Máxima Center (NL)
- Westmead Institute (AU)
Publication Details
- Journal
- Molecular Systems Biology
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1038/s44320-025-00152-y
- Primary Topic
- 3D Printing in Biomedical Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00