Ex vivo evaluation of tumor cell specific drug responses in malignant pleural effusions

// Carl-Olof Hillerdal 1 , Rita Otvos 1 , Tunde Szatmari 1 , Sulaf Abd Own 1 , Gunnar Hillerdal 2 , Asa-Lena Dackland 1 , Katalin Dobra 1 and Anders Hjerpe 1 1 Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology, Karolinska University Hospital, SE-141 86 Stockholm, Sweden 2 Gavle Hospital, Department of Lung Medicine, 803 24 Gavle, Sweden Correspondence to: Carl-Olof Hillerdal, email: carl-olof.hillerdal@ki.se Keywords: personalized medicine, drug sensitivity testing, malignant mesothelioma, lung cancer, pleural effusions Received: September 30, 2016     Accepted: August 25, 2017     Published: September 15, 2017 ABSTRACT The effect of chemotherapy may be improved by combining the most effective drugs based on testing the sensitivity of the individual tumor ex vivo . Such estimations of tumor cells from effusions have so far not been implemented in the clinical routine as a basis for individualized choice of therapy. One obstacle for such analyses is the admixture of benign cells that might obscure the results. In this paper we test and compare two ways of performing the analysis specifically on tumor cells. First we enrich the tumor cells, using antibody labeled magnetic separation, and measure the effects of subsequent drug exposure with the metabolic activity assays WST-1 and alamar blue. The second way of estimating drug effects specifically on tumor cells employs multi parameter flow cytometry, measuring apoptosis with the propidium iodide / AnnexinV technique and, particularly for pemetrexed, possible effects on cell cycle progression in immunologically identified tumor cells. The two techniques produce similar results, indicating a possible use in personalized medicine. The possible predictive role of the analysis remains to be shown.