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Rapid identification of optimal drug combinations for personalized cancer therapy using microfluidics

View ORCID ProfileFederica Eduati, Ramesh Utharala, Dharanija Madhavan, Ulf Peter Neumann, View ORCID ProfileThorsten Cramer, View ORCID ProfileJulio Saez-Rodriguez, View ORCID ProfileChristoph A. Merten
doi: https://doi.org/10.1101/093906
Federica Eduati
1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, UK
2European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg, Germany
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  • ORCID record for Federica Eduati
Ramesh Utharala
2European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg, Germany
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Dharanija Madhavan
2European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg, Germany
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Ulf Peter Neumann
3Department of Surgery, RWTH University Hospital, Aachen
4ESCAM – European Surgery Center Aachen Maastricht
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Thorsten Cramer
4ESCAM – European Surgery Center Aachen Maastricht
5Molecular Tumor Biology, Department Surgery, RWTH University Hospital, Aachen, Germany
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Julio Saez-Rodriguez
1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, UK
6Joint Research Centre for Computational Biomedicine (JRC-COMBINE), RWTH Aachen University, Faculty of Medicine, Aachen, Germany
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  • For correspondence: saezrodriguez@gmail.com merten@embl.de
Christoph A. Merten
2European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Meyerhofstrasse 1, Heidelberg, Germany
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  • ORCID record for Christoph A. Merten
  • For correspondence: saezrodriguez@gmail.com merten@embl.de
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Abstract

Functional screening of live patient cancer cells holds great potential for personalized medicine and allows to overcome the limited translatability of results from existing in-vitro and ex-vivo screening models. Here we present a plug-based microfluidics approach enabling the testing of drug combinations directly on cancer cells from patient biopsies. The entire procedure takes less than 48 hours after surgery and does not require ex vivo cultivation. We screened more than 1100 samples for different primary human tumors (each with 56 conditions and at least 20 replicates), and obtained highly specific sensitivity profiles. This approach allowed us to derive optimal treatment options which we further validated in two different pancreatic cancer cell lines. This workflow should pave the way for rapid determination of optimal personalized cancer therapies at assay costs of less than US$ 150 per patient.

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Posted December 14, 2016.
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Rapid identification of optimal drug combinations for personalized cancer therapy using microfluidics
Federica Eduati, Ramesh Utharala, Dharanija Madhavan, Ulf Peter Neumann, Thorsten Cramer, Julio Saez-Rodriguez, Christoph A. Merten
bioRxiv 093906; doi: https://doi.org/10.1101/093906
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Rapid identification of optimal drug combinations for personalized cancer therapy using microfluidics
Federica Eduati, Ramesh Utharala, Dharanija Madhavan, Ulf Peter Neumann, Thorsten Cramer, Julio Saez-Rodriguez, Christoph A. Merten
bioRxiv 093906; doi: https://doi.org/10.1101/093906

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