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

被引:24
|
作者
Chakrabarty, Sanjiban [1 ,2 ]
Quiros-Solano, William F. [3 ,4 ]
Kuijten, Maayke M. P. [1 ,5 ]
Haspels, Ben [1 ]
Mallya, Sandeep [6 ]
Lo, Calvin Shun Yu [1 ]
Othman, Amr [4 ]
Silvestri, Cinzia [4 ]
van de Stolpe, Anja [7 ]
Gaio, Nikolas [4 ]
Odijk, Hanny [1 ]
van de Ven, Marieke [8 ]
de Ridder, Corrina M. A. [9 ]
van Weerden, Wytske M. [9 ]
Jonkers, Jos [8 ]
Dekker, Ronald [3 ,7 ]
Taneja, Nitika [1 ]
Kanaar, Roland [1 ,5 ]
van Gent, Dik C. [1 ,5 ]
机构
[1] Erasmus MC, Erasmus MC Canc Inst, Dept Mol Genet, Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands
[2] Manipal Acad Higher Educ, Manipal Sch Life Sci, Dept Cell & Mol Biol, Manipal, Karnataka, India
[3] Delft Univ Technol, Dept Microelect Elect Components Technol & Mat, Delft, Netherlands
[4] BIOND Solut BV, Delft, Netherlands
[5] Erasmus MC, Oncode Inst, Rotterdam, Netherlands
[6] Manipal Acad Higher Educ, Manipal Sch Life Sci, Dept Bioinformat, Manipal, Karnataka, India
[7] Philips Res, Eindhoven, Netherlands
[8] Netherlands Canc Inst, Preclin Intervent Unit, Mouse Clin Canc & Ageing, Amsterdam, Netherlands
[9] Erasmus MC, Erasmus MC Canc Inst, Dept Urol, Rotterdam, Netherlands
基金
荷兰研究理事会; 欧盟地平线“2020”;
关键词
GENE-EXPRESSION; ALIGNMENT; THERAPY; MODELS; FLOW;
D O I
10.1158/0008-5472.CAN-21-0799
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:510 / 520
页数:11
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