TY - JOUR
T1 - A microfluidics platform for combinatorial drug screening on cancer biopsies
AU - Eduati, Federica
AU - Utharala, Ramesh
AU - Madhavan, Dharanija
AU - Neumann, Ulf Peter
AU - Longerich, Thomas
AU - Cramer, Thorsten
AU - Saez-Rodriguez, Julio
AU - Merten, Christoph A.
PY - 2018/6/22
Y1 - 2018/6/22
N2 - Screening drugs on patient biopsies from solid tumours has immense potential, but is challenging due to the small amount of available material. To address this, we present here a plug-based microfluidics platform for functional screening of drug combinations. Integrated Braille valves allow changing the plug composition on demand and enable collecting >1200 data points (56 different conditions with at least 20 replicates each) per biopsy. After deriving and validating efficient and specific drug combinations for two genetically different pancreatic cancer cell lines and xenograft mouse models, we additionally screen live cells from human solid tumours with no need for ex vivo culturing steps, and obtain highly specific sensitivity profiles. The entire workflow can be completed within 48 h at assay costs of less than US$ 150 per patient. We believe this can pave the way for rapid determination of optimal personalized cancer therapies.
AB - Screening drugs on patient biopsies from solid tumours has immense potential, but is challenging due to the small amount of available material. To address this, we present here a plug-based microfluidics platform for functional screening of drug combinations. Integrated Braille valves allow changing the plug composition on demand and enable collecting >1200 data points (56 different conditions with at least 20 replicates each) per biopsy. After deriving and validating efficient and specific drug combinations for two genetically different pancreatic cancer cell lines and xenograft mouse models, we additionally screen live cells from human solid tumours with no need for ex vivo culturing steps, and obtain highly specific sensitivity profiles. The entire workflow can be completed within 48 h at assay costs of less than US$ 150 per patient. We believe this can pave the way for rapid determination of optimal personalized cancer therapies.
KW - Animals
KW - Antineoplastic Combined Chemotherapy Protocols/pharmacology
KW - Biopsy
KW - Cell Line, Tumor
KW - Drug Screening Assays, Antitumor/economics
KW - Female
KW - High-Throughput Screening Assays/economics
KW - Humans
KW - Mice
KW - Microfluidics/economics
KW - Neoplasms/drug therapy
KW - Precision Medicine/methods
UR - http://www.scopus.com/inward/record.url?scp=85048985572&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-04919-w
DO - 10.1038/s41467-018-04919-w
M3 - Article
C2 - 29934552
AN - SCOPUS:85048985572
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2434
ER -