Microdissected tumor cuboids: a microscale cancer model for large-scale testing that retains a complex tumor
Biorxiv : the Preprint Server for Biology
|April 8, 2024
Summary
New "cuboid" microtissues from tumors accurately model the tumor microenvironment (TME). These models enable large-scale drug testing, including immunotherapy, aiding personalized cancer treatments and clinical trials.
Area of Science:
- Oncology
- Biotechnology
- Cancer Research
Background:
- Faithful human cancer models are needed to bridge the gap between laboratory research and clinical application.
- Existing models often fail to fully recapitulate the complex tumor microenvironment (TME).
- There is a demand for platforms that facilitate high-throughput drug screening within a relevant TME context.
Purpose of the Study:
- To evaluate the utility of microdissected tumor "cuboids" as a model for cancer research.
- To assess the ability of cuboids to retain key features of the TME.
- To determine the suitability of cuboids for drug and immunotherapy evaluation.
Main Methods:
- Development of a microdissection technique to generate cuboidal microtissues (cuboids) from tumor biopsies.
- Characterization of TME parameters in cuboids, including cellular architecture, cytokine secretion, and proteomics.
- Assessment of drug responses in cuboids using multi-well array drug panels and immunotherapy.
Main Results:
- Cuboids derived from mouse and human tumors successfully retained a complex TME.
- Cuboids maintained relevant TME parameters and demonstrated significant cytokine expression after culture.
- Cuboids exhibited robust responses to drug panels and immunotherapy, even after 7 days in culture.
Conclusions:
- Cuboids represent a faithful model for recapitulating the human TME and its response to therapeutics.
- This model system can provide crucial therapeutic information for personalized oncology.
- Cuboids hold potential for developing TME-dependent therapeutics, cancer disease models, and advancing clinical trials.
