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

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

  • iScience. 2022 Sep 6;25(10):105081. doi: 10.1016/j.isci.2022.105081.
Jia-Yang Chen 1 2 3,  Hsu-Huan Chou 4 5,  Syer Choon Lim 1,  Yen-Jang Huang 1 2 3,  Kuan-Chen Lai 6,  Chin-Lin Guo 7,  Chien-Yi Tung 8,  Chung-Tsai Su 9,  Jocelyn Wang 10,  Edward Liu 1 2,  Hsiao-Fen Han 11,  Po-Ying Yeh 1 2,  Chun-Mei Hu 1,  Alexander R Dunn 2,  Curtis W Frank 2,  Yi-Chun Wu 11 12 13,  Muh-Hwa Yang 1 6 8 14,  Ying-Chih Chang 1 2 3 15 16
Affiliations

Affiliations

  • 1 Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
  • 2 Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
  • 3 National Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, Taiwan.
  • 4 Department of General Surgery, Chang-Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan.
  • 5 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
  • 6 Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  • 7 Institute of Physics, Academia Sinica, Taipei 115, Taiwan.
  • 8 Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
  • 9 Atgenomix Inc., Taipei 105, Taiwan.
  • 10 The College, The University of Chicago, Chicago, IL 60637, USA.
  • 11 Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan.
  • 12 Center for Computational and Systems Biology, National Taiwan University, Taipei 106, Taiwan.
  • 13 Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan.
  • 14 Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan.
  • 15 Biomedical Translational Research Center, Academia Sinica, Taipei 115, Taiwan.
  • 16 Precision Health and Integrated Diagnostics Center, Stanford University, Stanford, CA 94305, USA.
PMID: 36204272 DOI: 10.1016/j.isci.2022.105081
Abstract

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.

Keywords

Cancer; Omics; Precision medicine; Transcriptomics.

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