Ex vivo tumor culture systems for functional drug testing and therapy response prediction

Titia G Meijer, Kishan At Naipal, Agnes Jager, Dik C van Gent, Titia G Meijer, Kishan At Naipal, Agnes Jager, Dik C van Gent

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.

Keywords: PDX; cancer-on-chip; cell culture; functional drug testing; organoids; organotypic tissue slices; personalized medicine.

Conflict of interest statement

Financial & competing interests disclosure The authors acknowledge grant support by the Netherlands Organization for Scientific Research (ZON-MW grant 40-42600-98-018) and The Netherlands Cancer Foundation KWF/Alpe d'HuZes (grant EMCR 2014-7048). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1. . Comparison of ex vivo…
Figure 1.. Comparison of ex vivo tumor culture techniques.
Fresh viable tumor tissue can be preserved and cultured ex vivo in several ways, each having its own advantages and disadvantages. A tumor sample can be dissociated using enzymatic and/or mechanical methods and subsequently cultured either as a 2D monolayer or in a 3D tumor spheroid culture. To mimic the in vivo situation as much as possible, dissected tumor samples can be implanted in immunodeficient mice to generate patient-derived xenograft models. Organotypic tumor tissue slices can be generated by precision slicing of a tumor specimen, keeping general tumor/tissue architecture intact. +: Advantages of the method; -: Disadvantages of the method.
Figure 2. . Main applications of different…
Figure 2.. Main applications of different ex vivo model systems.
An ex vivo model system should be chosen according to the purpose of the specific research. Each ex vivo model system has its own benefits and disadvantages, making one more applicable for a specific research endeavor than the others.

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