title: Culture and Drug Profiling of Patient Derived Malignant Pleural Effusions for Personalized Cancer Medicine.
abstract: BACKGROUND
  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 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.
  
  
  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.
authors.affiliation: Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Ruiz
authors.affiliation: Pharmaceutical Sciences, Roche Innovation Centre Basel, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kustermann
authors.affiliation: Pharmaceutical Sciences, Roche Innovation Centre Basel, Basel, Switzerland.
authors.forename: Elina
authors.initials: E
authors.lastname: Pietilae
authors.affiliation: Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Vlajnic
authors.affiliation: Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Betty
authors.initials: B
authors.lastname: Baschiera
authors.affiliation: Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Leila
authors.initials: L
authors.lastname: Arabi
authors.affiliation: Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lorber
authors.affiliation: Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Oeggerli
authors.affiliation: Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Spasenija
authors.initials: S
authors.lastname: Savic
authors.affiliation: Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Ellen
authors.initials: E
authors.lastname: Obermann
authors.affiliation: Pharmaceutical Sciences, Roche Innovation Centre Basel, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Singer
authors.affiliation: Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
authors.forename: Sacha I
authors.initials: SI
authors.lastname: Rothschild
authors.affiliation: Department of Medical Oncology, University Hospital Basel, Basel, Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Zippelius
authors.affiliation: Pharmaceutical Sciences, Roche Innovation Centre Basel, Basel, Switzerland.
authors.forename: Adrian B
authors.initials: AB
authors.lastname: Roth
authors.affiliation: Institute for Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D000077547:Crizotinib; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed / Q000494:pharmacology; D016066:Pleural Effusion, Malignant / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D057285:Precision Medicine / Q000379:methods*; D061251:Primary Cell Culture; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D011720:Pyrazoles; D011725:Pyridines; D000068437:Pemetrexed; D000077547:Crizotinib; D002945:Cisplatin