Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week

Yawei Hu, Xizhao Sui, Fan Song, Yaqian Li, Kaiyi Li, Zhongyao Chen, Fan Yang, Xiuyuan Chen, Yaohua Zhang, Xianning Wang, Qiang Liu, Cong Li, Binbin Zou, Xiaofang Chen (), Jun Wang () and Peng Liu ()
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Yawei Hu: Tsinghua University
Xizhao Sui: Peking University
Fan Song: Beihang University
Yaqian Li: Beihang University
Kaiyi Li: Tsinghua University
Zhongyao Chen: Tsinghua University
Fan Yang: Peking University
Xiuyuan Chen: Peking University
Yaohua Zhang: Beihang University
Xianning Wang: Beijing OrganoBio Corporation
Qiang Liu: Beijing Haidian Hospital
Cong Li: Beijing NeoAntigen Biotechnology Co. Ltd
Binbin Zou: Beijing NeoAntigen Biotechnology Co. Ltd
Xiaofang Chen: Beihang University
Jun Wang: Peking University
Peng Liu: Tsinghua University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract While the potential of patient-derived organoids (PDOs) to predict patients’ responses to anti-cancer treatments has been well recognized, the lengthy time and the low efficiency in establishing PDOs hamper the implementation of PDO-based drug sensitivity tests in clinics. We first adapt a mechanical sample processing method to generate lung cancer organoids (LCOs) from surgically resected and biopsy tumor tissues. The LCOs recapitulate the histological and genetic features of the parental tumors and have the potential to expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds of LCOs, a number that can be generated from most of the samples at passage 0, are sufficient to produce clinically meaningful drug responses within a week. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The LCO model coupled with the microwell device provides a technically feasible means for predicting patient-specific drug responses in clinical settings.

Date: 2021
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DOI: 10.1038/s41467-021-22676-1

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