Culture and drug profiling of patient derived malignant pleural effusions for personalized cancer medicine

Ruiz, C. and Kustermann, S. and Pietilae, E. and Vlajnic, T. and Baschiera, B. and Arabi, L. and Lorber, T. and Oeggerli, M. and Savic, S. and Obermann, E. and Singer, T. and Rothschild, S. I. and Zippelius, A. and Roth, A. B. and Bubendorf, L. (2016) Culture and drug profiling of patient derived malignant pleural effusions for personalized cancer medicine. PLoS ONE, 11 (8).

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Introduction The 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. Methods MPEs from patients with solid tumors were selected for this study. After morphological and molecular characterization, they were cultured in medium supplemented with patientderived sterile-filtered effusion supernatant. Growth characteristics were monitored in realtime 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. Results We 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. Conclusions We 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. © 2016 Ruiz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Item Type: Article
Additional Information: Cited By :5 Export Date: 16 February 2020 CODEN: POLNC
Uncontrolled Keywords: calretinin cisplatin epithelial cell adhesion molecule erlotinib pemetrexed thyroid transcription factor 1 antineoplastic agent crizotinib drug combination pyrazole derivative pyridine derivative Article carcinoma cell line cell proliferation cell separation controlled study culture medium cytostasis cytotoxicity epithelium cell ex vivo study human human cell human cell culture malignant pleura effusion molecular model mutational analysis personalized medicine solid tumor aged dose response drug screening immunomagnetic separation male metabolism middle aged pathology Pleural Effusion, Malignant primary cell culture procedures tumor cell culture Antineoplastic Agents Dose-Response Relationship, Drug Drug Combinations Drug Screening Assays, Antitumor Humans Precision Medicine Pyrazoles Pyridines Tumor Cells, Cultured
Subjects: QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib4 lib4
Date Deposited: 03 Mar 2020 11:12
Last Modified: 03 Mar 2020 11:12

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