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<p>Substantial evidence indicates that cancer stem cells (CSCs) drive breast cancer (BRC) initiation, progression, therapy resistance, recurrence and metastasis. Evaluating drug efficacy against patient-derived CSCs can advance precision oncology. However, high-throughput isolation of functional CSCs from small clinical samples remains challenging. Tumoursphere formation, arising from the clonal expansion of a single cancer cell, is a standard in vitro method for CSC assay and enrichment. Here we show a microwell cell-chip culture platform that enables rapid, high-throughput generation of uniform micro-tumourspheres (MTSs) from limited BRC specimens, such as puncture biopsies, facilitating functional CSC enrichment and personalized drug testing within 8 days. Single-cell transcriptomics and limiting dilution tumour initiation assay confirm that MTSs recapitulate CSC functionality, uniformity and heterogeneity. MTSs predicted clinical outcomes in 16 patients with BRC with ~93.8% accuracy, underscoring their translational potential for personalized drug testing. Overall, this platform provides a robust tool for CSC-targeted precision medicine.</p>

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High-throughput generation of patient-derived cancer stem cells for precision medicine using a microwell-chip platform

  • 期刊论文

  • 发表日期：

    2026年5月13日

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  • Zhe Zhao,
  • Jie Wang,
  • Xuan Xiong,
  • Sheng Zhang,
  • Mengdie Yang,
  • Hanfei Wu,
  • Xingzhi Liu,
  • Xinxing Ma,
  • Yan Chen,
  • Yong Qiao,
  • Junjun Cao,
  • Yan Mei,
  • Jun Yao,
  • Pan Du,
  • Yanlin Wu,
  • Guoqin Jiang,
  • Xin Zhao,
  • Quan Liu,
  • Zhongjuan Xu,
  • Hao Zhou,
  • Guangli Suo

摘要

Substantial evidence indicates that cancer stem cells (CSCs) drive breast cancer (BRC) initiation, progression, therapy resistance, recurrence and metastasis. Evaluating drug efficacy against patient-derived CSCs can advance precision oncology. However, high-throughput isolation of functional CSCs from small clinical samples remains challenging. Tumoursphere formation, arising from the clonal expansion of a single cancer cell, is a standard in vitro method for CSC assay and enrichment. Here we show a microwell cell-chip culture platform that enables rapid, high-throughput generation of uniform micro-tumourspheres (MTSs) from limited BRC specimens, such as puncture biopsies, facilitating functional CSC enrichment and personalized drug testing within 8 days. Single-cell transcriptomics and limiting dilution tumour initiation assay confirm that MTSs recapitulate CSC functionality, uniformity and heterogeneity. MTSs predicted clinical outcomes in 16 patients with BRC with ~93.8% accuracy, underscoring their translational potential for personalized drug testing. Overall, this platform provides a robust tool for CSC-targeted precision medicine.