Drug sensitivity profiling and molecular characteristics of cells from pleural effusions of patients with lung adenocarcinoma
Rita Ötvös1,2,*,Adam Szulkin1,*, Carl-Olof Hillerdal1, Aytekin Celep1, Eviane Yousef-Fadhel1, Henriette Skribek2, Anders Hjerpe1, László Székely2 and Katalin Dobra1
1 Karolinska Institutet, Department of Laboratory Medicine, Division of Pathology, Karolinska University Hospital, Stockholm, Sweden.
2 Karolinska Institutet, Department of Microbiology Tumor and Cell Biology (MTC), KI Solna Campus, Karolinska Institutet, Stockholm, Sweden.
* RÖ and AS contributed equally to this work.
Correspondence:
Rita Ötvös, email:
Keywords: Malignant pleural effusions, ex vivo chemo-sensitivity assay, RRM1, ERCC1
Received: February 11, 2015 Accepted: March 31, 2015 Published: April 1, 2015
Abstract
We propose to assess the therapeutic value of biomarker-guided individualized chemotherapy in patients with metastasizing lung adenocarcinoma. In this study, we used primary cells from pleural effusions from sixteen patients diagnosed with adenocarcinomas originating in the lung and from four patients with no malignant diagnosis. The ex vivo drug sensitivity of primary cells was assessed for 32 chemotherapeutical drugs. Linear regression analyses were performed to examine possible correlations between the drug sensitivity, overall survival and expression of ERCC1 and RRM1. The ex vivo drug sensitivity profiles of the patients revealed considerable heterogeneity in drug response. Vinblastine, vinorelbine, paclitaxel and actinomycin D showed high efficiency against 50% of the tested primary cells. Significant correlation was detected between the ex vivo sensitivity to platinum based drugs and gemcitabine and the level of ERCC1 and RRM1. No significant correlation was however seen between overall survival and drug sensitivity. The heterogeneity of the drug response suggests that optimal care of the adenocarcinoma patients should include the determination of drug sensitivity of the primary cells and would benefit to use personalized therapy.