A Microfluidic Cancer-on-Chip Platform Predicts Drug Response Using Organotypic Tumor Slice Culture

Sanjiban Chakrabarty, William F. Quiros-Solano, Maayke M.P. Kuijten, Ben Haspels, Sandeep Mallya, Calvin Shun Yu Lo, Amr Othman, Cinzia Silvestri, Anja van de Stolpe, Nikolas Gaio, Hanny Odijk, Marieke van de Ven, Corrina M.A. de Ridder, Wytske M. van Weerden, Jos Jonkers, Ronald Dekker, Nitika Taneja, Roland Kanaar, Dik C. van Gent

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Abstract

Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies. SIGNIFICANCE: The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.

Original languageEnglish
Pages (from-to)510-520
Number of pages11
JournalCancer Research
Volume82
Issue number3
DOIs
Publication statusPublished - 1 Feb 2022

Bibliographical note

Funding Information:
W.F. Quiros-Solano reports a patent for PCT/NL2017/050492 issued; in addition, W.F. Quiros-Solano is cofounder and holds equity in BIOND Solutions B.V. A. Othman is a Field Application Scientist at BIOND Solutions B.V. C. Silvestri reports a patent for PCT/NL2017/050492 issued; in addition, C. Silvestri is cofounder and Chief Executive Officer, and holds equity in BIOND Solutions B.V. N. Gaio reports grants from ECSEL Joint Undertaking during the conduct of the study; in addition, N. Gaio has a patent for PCT/NL2017/050492 issued; and is a cofounder and Chief Technology Officer, and holds equity in BIOND Solutions B.V. R. Kanaar reports grants from Dutch Research Council (NWO) and grants from Gravitation program CancerGenomiCs.nl from the NWO and is part of the Oncode Institute, which is partly financed by the Dutch Cancer Society during the conduct of the study.

Funding Information:
This work was supported by the KWF grant KWF11011, by the Gravitation program CancerGenomiCs.nl from the Dutch Research Council (NWO), the Oncode Institute, which is partly financed by the Dutch Cancer Society and the NWO (Building Blocks of Life grant 737.016.011). Part of this work is supported by Moore4Medical project funded by the ECSEL Joint Undertaking under grant number H2020-ECSEL-2019-IA-876190 (https://moore4medical.eu/).

Publisher Copyright:
© 2021 The Authors.

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