Multiomic characterization and drug testing establish circulating tumor cells as an ex vivo tool for personalized medicine
Jia-Yang Chen,
Hsu-Huan Chou,
Syer Choon Lim,
Yen-Jang Huang,
Kuan-Chen Lai,
Chin-Lin Guo,
Chien-Yi Tung,
Chung-Tsai Su,
Jocelyn Wang,
Edward Liu,
Hsiao-Fen Han,
Po-Ying Yeh,
Chun-Mei Hu,
Alexander R. Dunn,
Curtis W. Frank,
Yi-Chun Wu,
Muh-Hwa Yang,
Ying-Chih Chang
Affiliations
Jia-Yang Chen
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
Hsu-Huan Chou
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
Syer Choon Lim
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan
Yen-Jang Huang
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
Kuan-Chen Lai
Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Chin-Lin Guo
Institute of Physics, Academia Sinica, Taipei 115, Taiwan
Chien-Yi Tung
Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei 112, Taiwan
Chung-Tsai Su
Atgenomix Inc., Taipei 105, Taiwan
Jocelyn Wang
The College, The University of Chicago, Chicago, IL 60637, USA
Edward Liu
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA
Hsiao-Fen Han
Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 106, Taiwan
Po-Ying Yeh
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA
Chun-Mei Hu
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan
Alexander R. Dunn
Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA
Curtis W. Frank
Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA
Yi-Chun Wu
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; Corresponding author
Muh-Hwa Yang
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; Corresponding author
Ying-Chih Chang
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; Corresponding author
Summary: 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.
