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Circulating tumor cells as “liquid biopsies” to understand cancer metastasis

  • Dennis Woo
    Affiliations
    MD Program, University of Southern California, Los Angeles, California
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  • Min Yu
    Correspondence
    Reprint requests: Min Yu, Department of Stem Cell Biology and Regenerative Medicine, Harlyne J. Norris Cancer Research Tower, 1450 Biggy Street, NRT 3507, Los Angeles, CA 90033;
    Affiliations
    Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, California

    USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California
    Search for articles by this author
      Circulating tumor cells (CTCs) are a subset of cancer cells that are shed from the primary or metastatic tumors into the bloodstream. CTCs are responsible for the establishment of blood-borne distant metastases but their rarity, estimated at one CTC per billion blood cells, presents the biggest technical barrier to their functional studies. Recent advances in CTC isolation technology have allowed for the reliable capture of CTCs from the whole blood of cancer patients. The ability to derive clinically relevant information from CTCs isolated through a blood draw allows for the monitoring of active disease, avoiding the invasiveness inherent to traditional biopsy techniques. This review will summarize recent developments in CTC isolation technology; the development of CTC-derived models; the unique molecular characteristics of CTCs at the transcriptomic, genomic, and proteomic levels; and how these characteristics have been correlated to prognosis and therapeutic efficacy. Finally, we will summarize the recent findings on several signaling pathways in CTCs and metastasis. The study of CTCs is central to understanding cancer biology and promises a “liquid biopsy” that can monitor disease status and guide therapeutic management in real time.

      Abbreviations:

      ANGPTL4 (angiopoietin-like 4), CDX (CTC-derived xenograft), CK (cytokeratin), CNA (copy number alteration), CTC (circulating tumor cell), DAXX (death-associated protein 6), EMT (epithelial-mesenchymal transition), EpCAM (epithelial adhesion molecules), INDEL (insertion/deletion), JNK (c-Jun N-terminal kinases), MET (mesenchymal-epithelial transition), NSCLC (nonsmall cell lung cancer), PDX (patient-derived xenograft), PSA (prostate specific antigen), RNA-seq (RNA sequencing), SCLC (small cell lung cancer), SNV (single nucleotide variation), TGF-β (transforming growth factor beta)
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