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

Yawei Hu,Xiaofang Chen,Binbin Zou,Peng Liu,Yaqian Li,Xizhao Sui,Fan Song,Yaohua Zhang,Fan Yang,Xianning Wang,Xiuyuan Chen,Qiang Liu,Zhongyao Chen,Cong Li,Jun Wang,Kaiyi Li

doi:10.1038/s41467-021-22676-1

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.

Highlights

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
When the normal tissues were processed with the mechanical method, the normal lung tissue-derived spheroids (NLSs) were much less than the lung cancer organoids (LCOs) obtained from their corresponding tumors (Fig. 1b)
PDOs represent a new generation of in vitro tumor models that can be employed to predict the clinical outcomes of anticancer drugs for individual patients

Summary

Introduction

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. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The current PDO-based drug test still needs quite a few weeks or even months to provide results to patients This is mainly due to limited numbers of viable organoids derived from patient samples and the use of conventional cell culture techniques, which are operated in the microliter-scale volumes and require prolonged in vitro expansion to generate enough quantities of PDOs19. LCOs coupled with the InSMAR-chip may provide an efficient means for predicting patient-specific drug responses in lung cancer promptly

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Conclusion