Abstract
IntroductionThe use of patients’ own cancer cells for in vitro selection of the most promising treatment is an attractive concept in personalized medicine. Human carcinoma cells from malignant pleural effusions (MPEs) are suited for this purpose since they have already adapted to the liquid environment in the patient and do not depend on a stromal cell compartment. Aim of this study was to develop a systematic approach for the in-vitro culture of MPEs to analyze the effect of chemotherapeutic as well as targeted drugs.MethodsMPEs from patients with solid tumors were selected for this study. After morphological and molecular characterization, they were cultured in medium supplemented with patient-derived sterile-filtered effusion supernatant. Growth characteristics were monitored in real-time using the xCELLigence system. MPEs were treated with a targeted therapeutic (erlotinib) according to the mutational status or chemotherapeutics based on the recommendation of the oncologists.ResultsWe have established a robust system for the ex-vivo culture of MPEs and the application of drug tests in-vitro. The use of an antibody based magnetic cell separation system for epithelial cells before culture allowed treatment of effusions with only moderate tumor cell proportion. Experiments using drugs and drug-combinations revealed dose-dependent and specific growth inhibitory effects of targeted drugs.ConclusionsWe developed a new approach for the ex-vivo culture of MPEs and the application of drug tests in-vitro using real-time measuring of cell growth, which precisely reproduced the effect of clinically established treatments by standard chemotherapy and targeted drugs. This sets the stage for future studies testing agents against specific targets from genomic profiling of metastatic tumor cells and multiple drug-combinations in a personalized manner.
Highlights
The use of patients’ own cancer cells for in vitro selection of the most promising treatment is an attractive concept in personalized medicine
We developed a new approach for the ex-vivo culture of malignant pleural effusions (MPEs) and the application of drug tests in-vitro using real-time measuring of cell growth, which precisely reproduced the effect of clinically established treatments by standard chemotherapy and targeted drugs
There have been multiple studies testing in-vitro assays with patients’ cancer cells to select the optimal drug treatment for patients with various tumor types including lung cancer and ovarian cancer [3,4,5]. These chemotherapy sensitivity and resistance assays (CSRAs) have not proved to be sufficiently reliable for clinical routine. Most of these assays were based on culture of tissue specimens from solid tumors which poses several technical challenges such as contamination with normal nontumor cells or difficulties in disaggregation prior to culture which amongst other factors may have led to the observed lack of predictivity
Summary
The aim of this study was not the optimization of parameters for long-term culture of primary effusion cells, but their growth for a limited time period in order to perform the analyses and the drug experiments
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