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Significance of Studying Circulating Tumor Cells

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Circulating Tumor Cells

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

Circulating Tumor Cells (CTC) are tumor cells released into blood. They are considered the pivotal component of the metastatic cascade and are being extensively studied only in the last decade or so. Understanding the biological and clinical impact of CTC is likely to reveal important information of the metastatic process and contribute to better management of cancer. We briefly discuss here the current clinical utility of CTC and their emerging clinical applications.

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References

  1. Ashworth T (1869) A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J 14(3):146–149

    Google Scholar 

  2. Cristofanilli M et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351(8):781–791

    Article  CAS  PubMed  Google Scholar 

  3. Zheng S et al (2007) Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells. J Chromatogr A 1162(2):154–161

    Article  CAS  PubMed  Google Scholar 

  4. Gertler R et al (2003) Detection of circulating tumor cells in blood using an optimized density gradient centrifugation. In: Allgayer H (ed) Molecular staging of cancer. Springer, Berlin, pp 149–155

    Chapter  Google Scholar 

  5. Becker FF et al (1995) Separation of human breast cancer cells from blood by differential dielectric affinity. Proc Natl Acad Sci U S A 92(3):860–864

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. de Bono JS et al (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14(19):6302–6309

    Article  PubMed  Google Scholar 

  7. Cohen SJ et al (2009) Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol 20(7):1223–1229

    Article  CAS  PubMed  Google Scholar 

  8. Edge SB, Compton CC (2010) The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 17(6):1471–1474

    Article  PubMed  Google Scholar 

  9. Hayes DF et al (2006) Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 12(14 Pt 1):4218–4224

    Article  CAS  PubMed  Google Scholar 

  10. Budd GT et al (2006) Circulating tumor cells versus imaging—predicting overall survival in metastatic breast cancer. Clin Cancer Res 12(21):6403–6409

    Article  CAS  PubMed  Google Scholar 

  11. Goldkorn A et al (2014) Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase III trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. J Clin Oncol 32(11):1136–1142

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Scher H, Heller G, Molina A. Evaluation of a composite biomarker panel including circulating tumor cell (CTC) enumeration as a surrogate for survival in metastatic castration-resistant prostate cancer (mCRPC). Abstract No. 2861, The European Cancer Congress, Sept 27–Oct 1, 2013, Amsterdam, The Netherlands

    Google Scholar 

  13. Smerage JB et al (2014) Circulating tumor cells and response to chemotherapy in metastatic breast cancer: SWOG S0500. J Clin Oncol 32(31):3483–3489

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Alix-Panabières C, Pantel K (2014) Challenges in circulating tumour cell research. Nat Rev Cancer 14(9):623–631

    Article  PubMed  Google Scholar 

  15. Weinberg RA (2008) Leaving home early: reexamination of the canonical models of tumor progression. Cancer Cell 14(4):283–284

    Article  CAS  PubMed  Google Scholar 

  16. Podsypanina K et al (2008) Seeding and propagation of untransformed mouse mammary cells in the lung. Science 321(5897):1841–1844

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Rhim AD et al (2012) EMT and dissemination precede pancreatic tumor formation. Cell 148(1):349–361

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Pantel K et al (2012) Circulating epithelial cells in patients with benign colon diseases. Clin Chem 58(5):936–940

    Article  CAS  PubMed  Google Scholar 

  19. Rack B et al (2014) Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst. doi:10.1093/jnci/dju066

    PubMed Central  PubMed  Google Scholar 

  20. Saucedo-Zeni N et al (2012) A novel method for the in vivo isolation of circulating tumor cells from peripheral blood of cancer patients using a functionalized and structured medical wire. Int J Oncol 41(4):1241–1250

    PubMed Central  PubMed  Google Scholar 

  21. Fischer JC et al (2013) Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients. Proc Natl Acad Sci U S A 110(41):16580–16585

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Punnoose EA, Lackner MR (2012) Challenges and opportunities in the use of CTCs for companion diagnostic development. Recent Results Cancer Res 195:241–253

    Article  PubMed  Google Scholar 

  23. Powell AA et al (2012) Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS One 7(5):e33788

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Thiery JP (2002) Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2(6):442–454

    Article  CAS  PubMed  Google Scholar 

  25. Lin HK et al (2010) Portable filter-based microdevice for detection and characterization of circulating tumor cells. Clin Cancer Res 16(20):5011–5018

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Harouaka RA et al (2014) Flexible micro spring array device for high-throughput enrichment of viable circulating tumor cells. Clin Chem 60(2):323–333

    Article  CAS  PubMed  Google Scholar 

  27. Zhang L et al (2013) The identification and characterization of breast cancer CTCs competent for brain metastasis. Sci Transl Med 5(180):180ra48

    Article  PubMed  Google Scholar 

  28. Hofman V et al (2011) Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: comparison of the efficacy of the CellSearch Assay™ and the isolation by size of epithelial tumor cell method. Int J Cancer 129(7):1651–1660

    Google Scholar 

  29. Yu M et al (2013) Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science 339(6119):580–584

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Kang Y, Pantel K (2013) Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell 23(5):573–581

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Brabletz T (2012) To differentiate or not—routes towards metastasis. Nat Rev Cancer 12(6):425–436

    Article  CAS  PubMed  Google Scholar 

  32. Armstrong AJ et al (2011) Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res 9(8):997–1007

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Al-Hajj M et al (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A 100(7):3983–3988

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Balic M et al (2006) Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res 12(19):5615–5621

    Article  CAS  PubMed  Google Scholar 

  35. Theodoropoulos PA et al (2010) Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer. Cancer Lett 288(1):99–106

    Article  CAS  PubMed  Google Scholar 

  36. Baccelli I et al (2013) Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 31(6):539–544

    Article  CAS  PubMed  Google Scholar 

  37. Hou JM et al (2012) Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J Clin Oncol 30(5):525–532

    Article  PubMed  Google Scholar 

  38. Balic M et al (2013) Circulating tumor cells: from bench to bedside. Annu Rev Med 64:31–44

    Article  CAS  PubMed  Google Scholar 

  39. Adams DL et al (2014) Circulating giant macrophages as a potential biomarker of solid tumors. Proc Natl Acad Sci U S A 111(9):3514–3519

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Aceto N et al (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158(5):1110–1122

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Duda DG et al (2010) Malignant cells facilitate lung metastasis by bringing their own soil. Proc Natl Acad Sci U S A 107(50):21677–21682

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Kallergi G et al (2013) Apoptotic circulating tumor cells in early and metastatic breast cancer patients. Mol Cancer Ther 12(9):1886–1895

    Article  CAS  PubMed  Google Scholar 

  43. Smerage JB et al (2013) Monitoring apoptosis and Bcl-2 on circulating tumor cells in patients with metastatic breast cancer. Mol Oncol 7(3):680–692

    Article  CAS  PubMed  Google Scholar 

  44. Muller V et al (2005) Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin Cancer Res 11(10):3678–3685

    Article  PubMed  Google Scholar 

  45. Miles FL et al (2008) Stepping out of the flow: capillary extravasation in cancer metastasis. Clin Exp Metastasis 25(4):305–324

    Article  CAS  PubMed  Google Scholar 

  46. Paget S (1889) The distribution of secondary growths in cancer of the breast. Lancet 133(3421):571–573

    Article  Google Scholar 

  47. Kang Y et al (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3(6):537–549

    Article  CAS  PubMed  Google Scholar 

  48. Minn AJ et al (2007) Lung metastasis genes couple breast tumor size and metastatic spread. Proc Natl Acad Sci U S A 104(16):6740–6745

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Meng S et al (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10(24):8152–8162

    Article  PubMed  Google Scholar 

  50. Kim MY et al (2009) Tumor self-seeding by circulating cancer cells. Cell 139(7):1315–1326

    Article  PubMed Central  PubMed  Google Scholar 

  51. Shiozawa Y et al (2011) Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. J Clin Invest 121(4):1298–1312

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Miyamoto DT et al (2012) Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer. Cancer Discov 2(11):995–1003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Pailler E et al (2013) Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer. J Clin Oncol 31(18):2273–2281

    Article  PubMed  Google Scholar 

  54. Kwak EL et al (2010) Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 363(18):1693–1703

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Lohr JG et al (2014) Whole-exome sequencing of circulating tumor cells provides a window into metastatic prostate cancer. Nat Biotechnol 32(5):479–484

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Kirby BJ et al (2012) Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PLoS One 7(4):e35976

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Karabacak NM et al (2014) Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nat Protoc 9(3):694–710

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Zhou M-D et al (2014) Separable bilayer microfiltration device for viable label-free enrichment of circulating tumour cells. Sci Rep 4, 7392

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Gallant JN et al (2013) Predicting therapy response in live tumor cells isolated with the flexible micro spring array device. Cell Cycle 12(13):2132–2143

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Yu M et al (2014) Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 345(6193):216–220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Raimondi C et al (2014) Clinical utility of circulating tumor cell counting through Cell Search(®): the dilemma of a concept suspended in Limbo. Onco Targets Ther 7:619–625

    PubMed Central  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pathology & Laboratory Medicine, University of Miami Miller School of Medicine, Biomedical Research Building, #714, 1501 NW 10th Avenue, Miami, FL, 33136, USA

    Ram H. Datar M.Phil., Ph.D.

  2. Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Ram H. Datar M.Phil., Ph.D. & Richard J. Cote M.D., F.R.C.Path., F.C.A.P.

  3. The Dr. John T. MacDonald Foundation Biomedical Nanotechnology Institute, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Ram H. Datar M.Phil., Ph.D. & Richard J. Cote M.D., F.R.C.Path., F.C.A.P.

  4. Sheila and David Fuente Graduate Program in Cancer Biology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Zheng Ao Ph.D.

  5. Department of Pathology & Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA

    Richard J. Cote M.D., F.R.C.Path., F.C.A.P.

  6. Department of Pathology, Jackson Memorial Hospital, Miami, FL, USA

    Richard J. Cote M.D., F.R.C.Path., F.C.A.P.

Authors
  1. Ram H. Datar M.Phil., Ph.D.
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  2. Zheng Ao Ph.D.
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  3. Richard J. Cote M.D., F.R.C.Path., F.C.A.P.
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Corresponding author

Correspondence to Ram H. Datar M.Phil., Ph.D. .

Editor information

Editors and Affiliations

  1. Jackson Memorial Hospital, University of Miami, Miami, Florida, USA

    Richard J. Cote

  2. University of Miami, Miami, Florida, USA

    Ram H. Datar

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Datar, R.H., Ao, Z., Cote, R.J. (2016). Significance of Studying Circulating Tumor Cells. In: Cote, R., Datar, R. (eds) Circulating Tumor Cells. Current Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3363-1_1

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  • DOI: https://doi.org/10.1007/978-1-4939-3363-1_1

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-3361-7

  • Online ISBN: 978-1-4939-3363-1

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