Harnessing Next-Generation 3D Cancer Models to Elucidate Tumor-Microbiome Crosstalk

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The tumor microenvironment (TME) is a complex and dynamic ecosystem increasingly recognized for its interplay with the microbiome. In colorectal, breast, lung, liver, and brain cancers, bacterial communities and their metabolites are shown to influence tumor progression, immune responses, and therapeutic outcomes. To study these interactions in physiologically relevant contexts, advanced 3D in vitro models have emerged, including spheroids, organoids, microfluidic organ-on-a-chip platforms, and 3D-bioprinted constructs. These systems provide spatial organization, mechanical cues, and co-culture capabilities that facilitate investigation of host-microbiome-tumor cross-talk. Incorporation of live bacteria, their metabolites, and immune components into these platforms has yielded new insights into how the microbiome shapes cancer behavior, inflammation, and drug resistance. This review outlines recent advances in 3D model development for studying tumor-microbiome interactions, highlighting organ-specific applications, extracellular matrix-mimicking hydrogels, and biofabrication strategies. It also addresses key challenges, including maintaining microbiome viability, modeling temporal dynamics, and integrating immune complexity. Overcoming these limitations requires interdisciplinary approaches that merge bioengineering, microbiology, and oncology. Evolving 3D platforms offer power

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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