4.8 Article

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

Journal

CANCER RESEARCH
Volume 82, Issue 3, Pages 510-520

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-21-0799

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Funding

  1. KWF [KWF11011]
  2. Dutch Research Council (NWO)
  3. Oncode Institute - Dutch Cancer Society
  4. NWO [737.016.011]
  5. Moore4Medical project - ECSEL Joint Undertaking [H2020-ECSEL-2019-IA-876190]

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This study developed a microfluidic platform for evaluating cancer treatment response and predicting drug efficacy in breast and prostate tumors. By culturing tumor slices under controlled growth conditions, the platform allows reliable assessment of chemotherapeutic sensitivity and enables detailed mechanistic studies.
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.

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