Lung Cancer Organoids Analyzed on Microwell Arrays Predict Drug Responses of Patients Within a Week

Overview

Journal Nat Commun

Specialty Biology

Date 2021 May 11

PMID 33972544

Citations 100

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

Affiliations

Soon will be listed here.

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.

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References

Yu H, Steeghs N, Nijenhuis C, Schellens J, Beijnen J, Huitema A . Practical guidelines for therapeutic drug monitoring of anticancer tyrosine kinase inhibitors: focus on the pharmacokinetic targets. Clin Pharmacokinet. 2014; 53(4):305-25. DOI: 10.1007/s40262-014-0137-2. View

Cibulskis K, Lawrence M, Carter S, Sivachenko A, Jaffe D, Sougnez C . Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat Biotechnol. 2013; 31(3):213-9. PMC: 3833702. DOI: 10.1038/nbt.2514. View

Mou H, Vinarsky V, Tata P, Brazauskas K, Choi S, Crooke A . Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells. Cell Stem Cell. 2016; 19(2):217-231. PMC: 4975684. DOI: 10.1016/j.stem.2016.05.012. View

Boj S, Hwang C, Baker L, Chio I, Engle D, Corbo V . Organoid models of human and mouse ductal pancreatic cancer. Cell. 2015; 160(1-2):324-38. PMC: 4334572. DOI: 10.1016/j.cell.2014.12.021. View

Faust G, Hall I . SAMBLASTER: fast duplicate marking and structural variant read extraction. Bioinformatics. 2014; 30(17):2503-5. PMC: 4147885. DOI: 10.1093/bioinformatics/btu314. View

Zappasodi R, Merghoub T, Wolchok J . Emerging Concepts for Immune Checkpoint Blockade-Based Combination Therapies. Cancer Cell. 2018; 34(4):690. PMC: 6222254. DOI: 10.1016/j.ccell.2018.09.008. View

Lu Y, Sathasivam S, Song J, Crick C, Carmalt C, Parkin I . Repellent materials. Robust self-cleaning surfaces that function when exposed to either air or oil. Science. 2015; 347(6226):1132-5. DOI: 10.1126/science.aaa0946. View

Kondo J, Endo H, Okuyama H, Ishikawa O, Iishi H, Tsujii M . Retaining cell-cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer. Proc Natl Acad Sci U S A. 2011; 108(15):6235-40. PMC: 3076886. DOI: 10.1073/pnas.1015938108. View

Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernandez-Mateos J, Khan K . Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science. 2018; 359(6378):920-926. PMC: 6112415. DOI: 10.1126/science.aao2774. View

10.

Gao D, Vela I, Sboner A, Iaquinta P, Karthaus W, Gopalan A . Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014; 159(1):176-187. PMC: 4237931. DOI: 10.1016/j.cell.2014.08.016. View

11.

Li H, Durbin R . Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009; 25(14):1754-60. PMC: 2705234. DOI: 10.1093/bioinformatics/btp324. View

12.

Eisenhauer E, Therasse P, Bogaerts J, Schwartz L, Sargent D, Ford R . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2008; 45(2):228-47. DOI: 10.1016/j.ejca.2008.10.026. View

13.

Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen M . Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell. 2014; 160(1-2):299-312. PMC: 4313365. DOI: 10.1016/j.cell.2014.11.050. View

14.

Karnitz L, Flatten K, Wagner J, Loegering D, Hackbarth J, Arlander S . Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival. Mol Pharmacol. 2005; 68(6):1636-44. DOI: 10.1124/mol.105.012716. View

15.

Lee S, Hu W, Matulay J, Silva M, Owczarek T, Kim K . Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer. Cell. 2018; 173(2):515-528.e17. PMC: 5890941. DOI: 10.1016/j.cell.2018.03.017. View

16.

Granat L, Kambhampati O, Klosek S, Niedzwecki B, Parsa K, Zhang D . The promises and challenges of patient-derived tumor organoids in drug development and precision oncology. Animal Model Exp Med. 2019; 2(3):150-161. PMC: 6762043. DOI: 10.1002/ame2.12077. View

17.

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

18.

Zhang P, Zhang J, Bian S, Chen Z, Hu Y, Hu R . High-throughput superhydrophobic microwell arrays for investigating multifactorial stem cell niches. Lab Chip. 2016; 16(16):2996-3006. DOI: 10.1039/c6lc00331a. View

19.

Klionsky D, Emr S . Autophagy as a regulated pathway of cellular degradation. Science. 2000; 290(5497):1717-21. PMC: 2732363. DOI: 10.1126/science.290.5497.1717. View

20.

McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A . The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010; 20(9):1297-303. PMC: 2928508. DOI: 10.1101/gr.107524.110. View