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

• DOI: 10.1038/s41467-021-22676-1
• Publication Date: 2021-05-10T10:04:16Z
• Authors: 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; Peng Liu
• Keywords: Male; Organoid; 0301 basic medicine; Lung Neoplasms; Biopsy; Cell Culture Techniques; Computational biology; Mice; Engineering; Mice, Inbred NOD; Pathology; Internal medicine; Cancer; 3D Bioprinting Technology; Organoid Models; Q; Cell Cycle; Precision medicine; Gefitinib; Immunohistochemistry; 3. Good health; Organoids; Pharmaceutical Preparations; Oncology; Physical Sciences; Carcinoma, Squamous Cell; Medicine; Drug; Lung cancer; Pulmonary and Respiratory Medicine; Science; Biomedical Engineering; Antineoplastic Agents; Cancer research; Adenocarcinoma; FOS: Medical engineering; Article; 03 medical and health sciences; Cell Line, Tumor; Health Sciences; Genetics; Animals; Humans; Biology; Cell Proliferation; Pharmacology; Liquid biopsy; Xenograft Model Antitumor Assays; Cancer Stem Cells and Tumor Metastasis; FOS: Biological sciences; Drug Screening Assays, Antitumor; Pulmonary Calcification and Nodular Tumors in the Lung

AbstractWhile 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.