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  3. Precision Oncology for High-Grade Gliomas: A Tumor Organoid Model for Adjuvant Treatment Selection

Precision Oncology for High-Grade Gliomas: A Tumor Organoid Model for Adjuvant Treatment Selection

  • Bioengineering (Basel). 2025 Oct 19;12(10):1121. doi: 10.3390/bioengineering12101121.
Arushi Tripathy 1,  Sunjong Ji 2,  Habib Serhan 3,  Reka Chakravarthy Raghunathan 1,  Safiulla Syed 1,  Visweswaran Ravijumar 4,  Sunita Shankar 1,  Dah-Luen Huang 1,  Yazen Alomary 1,  Yacoub Haydin 1,  Tiffany Adam 2,  Kelsey Wink 2,  Nathan Clarke 5,  Carl Koschmann 2,  Nathan Merrill 3,  Toshiro Hara 1,  Sofia D Merajver 3,  Wajd N Al-Holou 1
Affiliations

Affiliations

  • 1 Department of Neurosurgery, University of Michigan, Ann Arbor, MI 48109, USA.
  • 2 Division of Hematology and Oncology, Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.
  • 3 Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
  • 4 Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  • 5 Division of Neuro-Oncology, Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
PMID: 41155119 DOI: 10.3390/bioengineering12101121
Abstract

High-grade gliomas (HGGs) are aggressive brain tumors with limited treatment options and poor survival outcomes. Variants including isocitrate dehydrogenase (IDH)-wildtype, IDH-mutant, and histone 3 lysine to methionine substitution (H3K27M)-mutant subtypes demonstrate considerable tumor heterogeneity at the genetic, cellular, and microenvironmental levels. This presents a major barrier to the development of reliable models that recapitulate tumor heterogeneity, allowing for the development of effective therapies. Glioma tumor organoids (GTOs) have emerged as a promising model, offering a balance between biological relevance and practical scalability for precision medicine. In this study, we present a refined methodology for generating three-dimensional, multiregional, patient-derived GTOs across a spectrum of glioma subtypes (including primary and recurrent tumors) while preserving the transcriptomic and phenotypic heterogeneity of their source tumors. We demonstrate the feasibility of a high-throughput drug-screening platform to nominate multi-drug regimens, finding marked variability in drug response, not only between patients and tumor types, but also across regions within the tumor. These findings underscore the critical impact of spatial heterogeneity on therapeutic sensitivity and suggest that multiregional sampling is critical for adequate glioma model development and drug discovery. Finally, regional differential drug responses suggest that multi-agent drug therapy may provide better comprehensive oncologic control and highlight the potential of multiregional GTOs as a clinically actionable tool for personalized treatment strategies in HGG.

Keywords

H3K27M mutation; IDH-mutant glioma; drug screening; high-grade glioma; patient-derived models; personalized medicine; precision oncology; spatial heterogeneity; translational bioengineering; tumor organoids.

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