The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
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Mangena, V., Chanoch-Myers, R. et al. Cancer Discovery. 15(2): 299-315. (2025).
doi: 10.1158/2159-8290.CD-23-1336.
Summary of the findings
Summary of the findingsHuman glioblastoma is characterized by intratumor heterogeneity and intercellular communications, yet existing in vitro models are limited in their capacity to model these important features, due to the lack of a structured tumor microenvironment. To address this limitation, the authors in this study developed a platform to grow patient-derived glioblastoma cells inside of cellularly-diverse human cortical organoids (i.e., GCOs), potentially recreating important interactions between malignant and non-malignant cells in the neuroglial microenvironment.
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The authors found that GCOs demonstrate an increased fidelity to glioblastoma cell states found in patient tumors, demonstrating the clinical relevance of this modeling approach. Unexpectedly, they further observed that tumor cells in the GCO models carry out widespread transfer of malignant mRNAs to non-malignant cells in the tumor microenvironment. The authors used single-cell RNA-sequencing to dissect the identities of these transcripts, and show that this transfer is biased towards particular malignant and non-malignant populations, especially astrocyte-like cells. The mechanism of this communication involves extracellular vesicles, with possible synergistic contributions from membrane nano/microtube intercellular networks.
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Future impact
The scale of intercellular mRNA transfer described in this work has not been previously appreciated and raises multiple exciting points. First, the authors show that intercellular mRNA transfer extends to non-glioblastoma cancer organoid models, suggesting that this transfer may represent a more fundamental principle of microenvironmental crosstalk across many human cancers. Second, the study demonstrates the unique value of modeling tumors in 3D organoid constructs to better recreate integrated tumor microenvironments and complex disease biology. Ultimately, better tumor models and increased understanding of microenvironmental dynamics will improve the translation of novel cancer therapies.
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