Multiomic characterization and drug testing establish circulating tumor cells as an ex vivo tool for personalized medicine.

Autor:	Chen JY; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.; National Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, Taiwan., Chou HH; Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan.; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan., Lim SC; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan., Huang YJ; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.; National Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, Taiwan., Lai KC; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan., Guo CL; Institute of Physics, Academia Sinica, Taipei 115, Taiwan., Tung CY; Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan., Su CT; Atgenomix Inc., Taipei 105, Taiwan., Wang J; The College, The University of Chicago, Chicago, IL 60637, USA., Liu E; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA., Han HF; Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan., Yeh PY; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA., Hu CM; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan., Dunn AR; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA., Frank CW; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA., Wu YC; Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan.; Center for Computational and Systems Biology, National Taiwan University, Taipei 106, Taiwan.; Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan., Yang MH; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.; Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.; Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan., Chang YC; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.; National Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, Taiwan.; Biomedical Translational Research Center, Academia Sinica, Taipei 115, Taiwan.; Precision Health and Integrated Diagnostics Center, Stanford University, Stanford, CA 94305, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2022 Sep 06; Vol. 25 (10), pp. 105081. Date of Electronic Publication: 2022 Sep 06 (Print Publication: 2022).
DOI:	10.1016/j.isci.2022.105081
Abstrakt:	Matching the treatment to an individual patient's tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells. CTCs and metastatic cells, but not primary tumor cells, shared stochastic mutations and similar hypomethylation levels at transcription start sites. CTCs and metastatic tumor cells shared a hybrid epithelial/mesenchymal transcriptome state with reduced adhesive and enhanced mobilization characteristics. We tested anti-cancer drugs on tumor cells from a metastatic breast cancer patient. CTC responses mirrored the impact of drugs on metastatic rather than primary tumors. Our multiomic and clinical anti-cancer drug response results reveal that CTCs resemble metastatic tumors and establish CTCs as an ex vivo tool for personalized medicine. Competing Interests: Ying-Chih Chang is the founder and stockholder of Acrocyte Therapeutics Inc., New Taipei City, Taiwan. Other authors declare no conflicts of interest. (© 2022 The Authors.)
Databáze:	MEDLINE
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