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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

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.

More about this publication

Cancer research

Volume 82
Issue nr. 3
Pages 510-520
Publication date 01-02-2022

Full text links

Publisher website (DOI) 10.1158/0008-5472.CAN-21-0799
Europe PubMed Central 34872965
Pubmed 34872965

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