other · HAL (Le Centre pour la Communication Scientifique Directe)
Existing three-dimensional cancer models such as spheroids and organoids often fail to reproduce the complex microenvironment of tumours, limiting their ability to reflect differences between individual patients. To address this, a scaffold-free 3D breast cancer culture model called patient-derived tumorospheres was created from fresh surgical tissue. Analysis confirmed that these models match their original tumours in molecular markers and the presence of immune and endothelial cells. The cultured spheres also produce their own extracellular matrix components and retain the structural heterogeneity and spectroscopic features of native tissue. Testing with the chemotherapy drug paclitaxel showed that cell death increased with higher doses and longer exposure times. The results demonstrate an ex vivo system that preserves primary tumour characteristics rapidly and without artificial matrices.
Laboratory cancer research often relies on animal models or simple cell cultures that fail to mimic human tissue accurately. By creating three-dimensional tumour models that faithfully preserve a patient's specific tumour microenvironment, researchers can test treatments against realistic cancer biology. This approach supports personalised medicine development while actively helping to reduce dependence on animal testing in preclinical research.
This research is at an early methodological stage. It could enable drug developers, oncology researchers, and preclinical testing facilities to screen therapeutic responses and explore personalised oncology strategies on patient-matched tissues. By providing a rapid, scaffold-free testing platform, the approach offers a laboratory tool for preclinical drug evaluation that could eventually reduce animal testing requirements.
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Patient-derived spheroids and organoids are increasingly used in cancer research to reduce animal experimentation and enhance reproducibility. However, these models do not recapitulate the tumor microenvironment, which prevents from taking interpatient variability into account. To overcome this limitation, we developed a patient-derived 3D breast cancer model from fresh surgical specimens, termed patient-derived tumorosphere (PDTs). Immunohistochemistry revealed strong concordance in molecular markers, as well as in immune and endothelial cell representation, between PDTs and their corresponding primary tumors. Second harmonic generation and autofluorescence microscopy confirmed de novo synthesis of extracellular matrix components. Infrared micro-spectroscopy combined with K-means clustering revealed structural heterogeneity within PDTs but morpho-spectroscopic similarity to native tissue. Drug-response assays with paclitaxel suggested increased cytotoxicity with drug concentrations and exposure time. This preliminary methodological study indicates that PDTs retain cellular heterogeneity and extracellular-matrix-associated signals from the parental tumors, highlighting their potential as a rapid and scaffold-free relevant model for personalized therapy research and reduction of animal use in preclinical studies.
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DOI: 10.60675/krk9-zs80/sn20260821-15r/short-notes
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