Prostate Cancer Patient‐Derived Organoids (PDOs) as Functional Avatars for Antisense Oligonucleotide (ASO)‐Based Personalized Therapy
7 affiliations
- 1INSERM ERL U1326 CINaM CERIMED CNRS UMR 7325 Aix‐Marseille University Marseille France
- 2Department of Urology Hospital Nord, AP‐HM Aix‐Marseille University Marseille France
- 3Laboratoire d'Anatomie et Cytologie Pathologiques, Hôpital de la Timone, AP‐HM Marseille France
- 4European Center for Research in Medical Imaging (CERIMED) Aix‐Marseille University Marseille France
- 5University of Burgundy Europe, INSERM UMR 1231, HSP‐Pathies Centre for Translational and Molecular Medicine Dijon France
- 6University of Burgundy Europe Centre Georges‐François Leclerc (CGFL) Dijon France
- 7Department of Nuclear Medicine Hôpital de la Timone, AP‐HM, Aix‐Marseille University Marseille France
Abstract
Patient‐derived tumor organoids (PDOs) closely preserve the cellular heterogeneity, histopathology, and molecular features of the original tumors, making them powerful preclinical models. Antisense oligonucleotides (ASOs) are an emerging class of precision medicines that modulate gene expression at the RNA level with high target specificity, yet their application in organoid systems remains underexplored. Here, we adapted previously described protocols to establish a biobank of prostate cancer (PC) PDOs, achieving a high initial growth success rate (>90%). Histological and molecular analyses confirmed the preservation of key tumor features. Using these models, we assessed several ASOs, with particular emphasis on OGX‐427 (Apatorsen), an ASO targeting heat shock protein 27 (HSP27) that has been evaluated in phase I/II clinical trials. While OGX‐427 effectively suppressed HSP27 expression and inhibited cell growth in 2D cultures, its efficacy was markedly limited in 3D organoids, likely due to extracellular matrix and structural barriers. Removing Matrigel and applying single‐cell transfection overcame these barriers, achieving efficient ASO uptake, significant target protein downregulation, and robust, dose‐dependent inhibition of organoid growth. These findings underscore the utility of PDOs for evaluating ASO‐based therapies and their potential to accelerate precision oncology strategies for PC and other malignancies.
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BibTeX
@article{tran2026prostate,
title = {{Prostate Cancer Patient‐Derived Organoids (PDOs) as Functional Avatars for Antisense Oligonucleotide (ASO)‐Based Personalized Therapy}},
author = {Thi Thom Tran and Thi Tu Uyen Phan and Michael Baboudjian and Quang Hieu Duong and Ines Sousa and Thi Thuy Le and Virginie Baylot and Sophie Giusiano and Laurent Daniel and Pauline Brige and Benjamin Guillet and Cyrille Bastide and Carmen Garrido and David Taïeb and Thi Khanh Le and Palma Rocchi},
journal = {Advanced Healthcare Materials},
year = {2026},
month = oct,
doi = {10.1002/adhm.202505251},
url = {https://doi.org/10.1002/adhm.202505251},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Prostate Cancer Patient‐Derived Organoids (PDOs) as Functional Avatars for Antisense Oligonucleotide (ASO)‐Based Personalized Therapy
AU - Thi Thom Tran
AU - Thi Tu Uyen Phan
AU - Michael Baboudjian
AU - Quang Hieu Duong
AU - Ines Sousa
AU - Thi Thuy Le
AU - Virginie Baylot
AU - Sophie Giusiano
AU - Laurent Daniel
AU - Pauline Brige
AU - Benjamin Guillet
AU - Cyrille Bastide
AU - Carmen Garrido
AU - David Taïeb
AU - Thi Khanh Le
AU - Palma Rocchi
PY - 2026
DA - 2026/10/11
JO - Advanced Healthcare Materials
DO - 10.1002/adhm.202505251
UR - https://doi.org/10.1002/adhm.202505251
AB - Patient‐derived tumor organoids (PDOs) closely preserve the cellular heterogeneity, histopathology, and molecular features of the original tumors, making them powerful preclinical models. Antisense oligonucleotides (ASOs) are an emerging class of precision medicines that modulate gene expression at the RNA level with high target specificity, yet their application in organoid systems remains underexplored. Here, we adapted previously described protocols to establish a biobank of prostate cancer (PC) PDOs, achieving a high initial growth success rate (>90%). Histological and molecular analyses confirmed the preservation of key tumor features. Using these models, we assessed several ASOs, with particular emphasis on OGX‐427 (Apatorsen), an ASO targeting heat shock protein 27 (HSP27) that has been evaluated in phase I/II clinical trials. While OGX‐427 effectively suppressed HSP27 expression and inhibited cell growth in 2D cultures, its efficacy was markedly limited in 3D organoids, likely due to extracellular matrix and structural barriers. Removing Matrigel and applying single‐cell transfection overcame these barriers, achieving efficient ASO uptake, significant target protein downregulation, and robust, dose‐dependent inhibition of organoid growth. These findings underscore the utility of PDOs for evaluating ASO‐based therapies and their potential to accelerate precision oncology strategies for PC and other malignancies.
SN - 2192-2640
SN - 2192-2659
ER -