3D models to capture and perturb tumour heterogeneity in vitro.

3D tumour models now enable controlled perturbations of cancer-cell and microenvironmental heterogeneity across multiple scales, addressing a key gap in capturing real tumour diversity.

• Why it matters: Simplified, homogeneous in vitro systems miss the spatial and biological diversity of human tumours, limiting insight into metastasis, resistance, and relapse.
• What they did: This Review surveys current 3D platforms and maps which heterogeneity dimensions they recapitulate and which perturbations they support, including genetic programmes, therapy responses, transport, matrix mechanics, oxygenation, perfusion, and stromal–immune interactions.
• The result: The field is progressing toward dynamic, multiscale, mechanistic testing, but challenges remain in fidelity, standardization, scalability, longitudinal readouts, and clinical predictability.

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