Ex Vivo Tumor Culture Systems for Functional Drug Testing and Therapy Response Prediction

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.

Precision Oncology: The Road Ahead

“…The biggest advantage of these culture types is that they retain cancer associated stromal cells, preserve tumor–stroma interactions, signaling pathways and gene expression profiles [211]. Improvements include the use of autologous serum and patient-specific stromal-matrix proteins to more closely resemble individual microenvironmental conditions [212], aiming to accurately predict responses to anticancer drugs.…”

“…soft, mucinous or fatty tissue), where firm tissue consistency is required [213, 214]. Another drawback of slice cultures is the loss of viability within 5 to 7 days [211]. As the median time frame for molecular profiling and data processing in precision oncology trials is 2–4 weeks, the method is not suitable for testing genomics-guided therapies derived from the same biopsy, unless combined with other models.…”

Bringing benign ectomesenchymal odontogenic tumours to the lab: An in vitro study using an organotypic culture model

“…The cancer theory that focuses on tumour microenvironment advocates that mutations alone do not lead the course and progression of lesions . In ex vivo conditions, the reproduction of the microenvironment of neoplasms in three‐dimensional culture models can be helpful to obtain more accurate responses and predictable results in several different experiments that can be carried out …”

“…Organotypic cell culture corresponds to co‐cultures (ie tumour and stromal cells) that aim to mimic the conditions of parenchyma and stromal interactions. We used the direct explant technique, which favours the maintenance of the tumoural complexity, as the tumour cells are surrounded by their original microenvironment . There are a few limitations of the model we propose, including the availability of enough tissue to be used in culture, the risk of explant contamination (even when antibiotics and antimycotics are used) and cell senescence, which limits large‐scale cell culture studies.…”

Precision Medicine in Oncology: In Vitro Drug Sensitivity and Resistance Test (DSRT) for Selection of Personalized Anticancer Therapy

“…However, there are some drawbacks of xenograft models, which restrict their clinical applications for making decisions about the appropriate therapy. First, the success rate of establishing of a xenograft is low; second, the time of establishing varies from 2 to 12 months; third, this method is very costly and not compatible with high throughput required in precision medicine Tumor tissue slices are thin slices of a tumor that are tested in microtiter plates with different compounds.…”