Abstract
Optimal patient stratification is of utmost importance in the era of personalized medicine. Prediction of individual treatment responses by functional ex vivo assays requires model systems derived from viable tumor samples, which should closely resemble in vivo tumor characteristics and microenvironment. This review discusses a broad spectrum of model systems, ranging from classic 2D monolayer culture techniques to more experimental ‘cancer-on-chip’ procedures. We mainly focus on organotypic tumor slices that take tumor heterogeneity and tumor–stromal interactions into account. These 3D model systems can be exploited for patient selection as well as for fundamental research. Selection of the right model system for each specific research endeavor is crucial and requires careful balancing of the pros and cons of each technology.
Highlights
Organotypic tissue sliceUsing primary (tumor) cell cultures in low passages for diagnostic testing, but is a major concern for extended culturing of cell lines in a laboratory setting
High-throughput drug screening requires 2D or 3D tumor cell cultures, whereas patient-derived xenograft models are useful for validation purposes
Organotypic tissue slices reflect intratumor heterogeneity and tumor–stromal interactions of in vivo tumors. Functional assays on organotypic tissue slices can be evaluated in a few days to weeks, making them suitable for drug selection in the personalized medicine era
Summary
Using primary (tumor) cell cultures in low passages for diagnostic testing, but is a major concern for extended culturing of cell lines in a laboratory setting. Tumor organoids derived from a homogenous population of stem cells do not harbor the microenvironment of in vivo tumors, which include nontransformed cells such as stromal fibroblasts and infiltrating immune cells This technique can be developed further by introducing additional heterogeneity through patient-matched co-cultures with organoids grown from normal tissue adjacent to the tumor. 3D organoid cultures are valuable tools for drug screens, biomarker discovery and studies on drug resistance mechanisms This model lacks the complexity of the tumor microenvironment and is less suited to guide personalized medicine. Systematic analysis of PDX models enables biobanking of genomically well-defined tumors [34] These biobanks are valuable resources for developing new predictive or prognostic biomarkers and individualized treatment strategies, thereby potentially guiding personalized medicine [42]. This leads to a model system in which the tumor cells are surrounded by their original microenvironment, rather than artificial matrices
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