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Background <p>Three dimensional (3D) cell cultures can be effectively used for drug discovery and development but there are still challenges in their general application to high-throughput screening. In this study, we developed a novel high-throughput chemotherapeutic 3D drug screening system for gastric cancer, named 'Cure-GA', to discover clinically applicable anticancer drugs and predict therapeutic responses.</p> Methods <p>Primary cancer cells were isolated from 143 fresh surgical specimens by enzymatic treatment. Cell-Matrigel mixtures were automatically printed onto the micropillar surface then stabilized in an optimal culture medium for 3 days to form tumoroids. These tumoroids were exposed in the drug-containing media for 7 days. Cell viability was measured by fluorescence imaging and adenosine triphosphate assays. On average, 0.31&#xa0;±&#xa0;0.23&#xa0;g of fresh tumor tissue yielded 4.05×10<sup>6</sup> ± 4.38×10<sup>6</sup> viable cells per sample.</p> Results <p>Drug response results were successfully acquired from 103 gastric cancer tissues (success rate = 72%) within 13&#xa0;±&#xa0;2 days, averaging 6.4&#xa0;±&#xa0;2.7 results per sample. Pearson correlation analysis showed viable cell numbers significantly impacted drug data acquisition (<i>p&#xa0;</i>&lt;&#xa0;0.00001). Tumoroids retained immunohistochemical characteristics, mutation signatures, and gene expression consistent with primary tumors. Drug reactivity data enabled prediction of synergistic drug correlations. Additionally, a multiparameter index-based prognosis model for patients undergoing gastrectomy followed by adjuvant XELOX was developed, showing significant differences in 1-year recurrence-free survival rates between drug responders and non-responders (<i>p</i>&#xa0;&lt;&#xa0;0.0001).</p> Conclusions <p>The Cure-GA platform enables rapid evaluation of chemotherapeutic responses using patient-derived tumoroids, providing clinicians with crucial insights for personalized treatment strategies and improving therapeutic outcomes.</p>

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High-Throughput Chemotherapeutic Drug Screening System for Gastric Cancer (Cure-GA)

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月23日

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  • Jieun Lee,
  • In Hee Kim,
  • Donghyeok Seol,
  • Sangjun Lee,
  • Mira Yoo,
  • Tae-Kyeong Lee,
  • So Hee Yoon,
  • Eunju Lee,
  • Duyeong Hwang,
  • So Hyun Kang,
  • Young Suk Park,
  • Bosung Ku,
  • Sang Youl Jeon,
  • Yongmun Choi,
  • Keehoon Jung,
  • Ji-Won Kim,
  • Jin Won Kim,
  • Sang-Hoon Ahn,
  • Keun-Wook Lee,
  • Hyung-Ho Kim,
  • Hyeon Jeong Oh,
  • Dong Woo Lee,
  • Yun-Suhk Suh

摘要

Background

Three dimensional (3D) cell cultures can be effectively used for drug discovery and development but there are still challenges in their general application to high-throughput screening. In this study, we developed a novel high-throughput chemotherapeutic 3D drug screening system for gastric cancer, named 'Cure-GA', to discover clinically applicable anticancer drugs and predict therapeutic responses.

Methods

Primary cancer cells were isolated from 143 fresh surgical specimens by enzymatic treatment. Cell-Matrigel mixtures were automatically printed onto the micropillar surface then stabilized in an optimal culture medium for 3 days to form tumoroids. These tumoroids were exposed in the drug-containing media for 7 days. Cell viability was measured by fluorescence imaging and adenosine triphosphate assays. On average, 0.31 ± 0.23 g of fresh tumor tissue yielded 4.05×106 ± 4.38×106 viable cells per sample.

Results

Drug response results were successfully acquired from 103 gastric cancer tissues (success rate = 72%) within 13 ± 2 days, averaging 6.4 ± 2.7 results per sample. Pearson correlation analysis showed viable cell numbers significantly impacted drug data acquisition (p < 0.00001). Tumoroids retained immunohistochemical characteristics, mutation signatures, and gene expression consistent with primary tumors. Drug reactivity data enabled prediction of synergistic drug correlations. Additionally, a multiparameter index-based prognosis model for patients undergoing gastrectomy followed by adjuvant XELOX was developed, showing significant differences in 1-year recurrence-free survival rates between drug responders and non-responders (p < 0.0001).

Conclusions

The Cure-GA platform enables rapid evaluation of chemotherapeutic responses using patient-derived tumoroids, providing clinicians with crucial insights for personalized treatment strategies and improving therapeutic outcomes.