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Circulating Tumor Cells: A Noninvasive Liquid Biopsy in Cancer

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Book cover Molecular Testing in Cancer

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Abstract

Circulating tumor cells (CTC) currently hold a great promise as a noninvasive “liquid biopsy” and their analysis has emerged as one of the hottest fields in cancer research. The clinical significance of CTC in peripheral blood has already been shown in many types of solid cancers such as breast, colorectal, and prostate. CTC enumeration in peripheral blood is widely used as an early marker of response to systemic therapy and is FDA-cleared in metastatic breast, colorectal, and prostate cancer. CTC molecular characterization has a strong potential to be translated into individualized targeted treatments and spares cancer patients ineffective therapies. Moreover, molecular characterization of CTC as a whole or even at the single cell level can elucidate their connection to cancer stem cells and provide new insights into the complex biology of metastasis and therapy resistance mechanisms. An in-depth understanding of the biological nature of these cells could possibly lead to the discovery of novel molecular targets for cancer therapeutics. Here, we summarize the recent advances in the clinical applications of CTC analysis in breast, colorectal, and prostate cancer and the latest developments in their molecular characterization.

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References

  1. Ashworth TR. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Med J Aust. 1869;14:146–7.

    Google Scholar 

  2. Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.

    Article  CAS  PubMed  Google Scholar 

  3. Alix-Panabieres C, Pantel K. Circulating tumor cells: liquid biopsy of cancer. Clin Chem. 2013;59:110–8.

    Article  CAS  PubMed  Google Scholar 

  4. Lianidou ES, Markou A. Circulating tumor cells as emerging tumor biomarkers in breast cancer. Clin Chem Lab Med. 2011;49:1579–90.

    Article  CAS  PubMed  Google Scholar 

  5. Pantel K, Alix-Panabieres C, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol. 2009;6:339–51.

    Article  CAS  PubMed  Google Scholar 

  6. Aguirre-Ghiso JA, Bragado P, Sosa MS. Metastasis awakening: targeting dormant cancer. Nat Med. 2013;19:276–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Polzer B, Klein CA. Metastasis awakening: the challenges of targeting minimal residual cancer. Nat Med. 2013;19:274–5.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang L, Riethdorf S, Wu G, Wang T, Yang K, Peng G, et al. Meta-analysis of the prognostic value of circulating tumor cells in breast cancer. Clin Cancer Res. 2012;18:5701–10.

    Article  PubMed  Google Scholar 

  9. Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.

    Article  CAS  PubMed  Google Scholar 

  10. Pierga JY, Hajage D, Bachelot T, Delaloge S, Brain E, Campone M, et al. High independent prognostic and predictive value of circulating tumor cells compared with serum tumor markers in a large prospective trial in first-line chemotherapy for metastatic breast cancer patients. Ann Oncol. 2012;23:618–24.

    Article  PubMed  Google Scholar 

  11. Giordano A, Egleston BL, Hajage D, Bland J, Hortobagyi GN, Reuben JM, et al. Establishment and validation of circulating tumor cell-based prognostic nomograms in first-line metastatic breast cancer patients. Clin Cancer Res. 2013;19:1596–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Giordano A, Cristofanilli M. CTCs in metastatic breast cancer. Recent Results Cancer Res. 2012;195:193–201.

    Article  PubMed  Google Scholar 

  13. Muller V, Riethdorf S, Rack B, Janni W, Fasching PA, Solomayer E, et al. Prognostic impact of circulating tumor cells assessed with the Cell Search System and AdnaTest Breast in metastatic breast cancer patients: the DETECT study. Breast Cancer Res. 2012;14:R118.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wallwiener M, Hartkopf AD, Baccelli I, Riethdorf S, Schott S, Pantel K, et al. The prognostic impact of circulating tumor cells in subtypes of metastatic breast cancer. Breast Cancer Res Treat. 2013;137:503–10.

    Article  PubMed  Google Scholar 

  15. Bidard FC, Fehm T, Ignatiadis M, Smerage JB, Alix-Panabieres C, Janni W, et al. Clinical application of circulating tumor cells in breast cancer: overview of the current interventional trials. Cancer Metastasis Rev. 2013;32(1–2):179–88.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.

    Article  CAS  PubMed  Google Scholar 

  17. Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353:793–802.

    Article  CAS  PubMed  Google Scholar 

  18. Braun S, Hepp F, Sommer HL, Pantel K. Tumor-antigen heterogeneity of disseminated breast cancer cells: implications for immunotherapy of minimal residual disease. Int J Cancer. 1999;84:1–5.

    Article  CAS  PubMed  Google Scholar 

  19. Klein CA, Schmidt-Kittler O, Schardt JA, Pantel K, Speicher MR, Riethmuller G. Comparative genomic hybridization, loss of heterozygosity, and DNA sequence analysis of single cells. Proc Natl Acad Sci U S A. 1999;96:4494–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Synnestvedt M, Borgen E, Wist E, Wiedswang G, Weyde K, Risberg T, et al. Disseminated tumor cells as selection marker and monitoring tool for secondary adjuvant treatment in early breast cancer. Descriptive results from an intervention study. BMC Cancer. 2012;12:616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Synnestvedt M, Borgen E, Schlichting E, Schirmer CB, Renolen A, Giercksky KE, et al. Disseminated tumour cells in the bone marrow in early breast cancer: morphological categories of immunocytochemically positive cells have different impact on clinical outcome. Breast Cancer Res Treat. 2013;138:485–97.

    Article  CAS  PubMed  Google Scholar 

  22. Mathiesen RR, Borgen E, Renolen A, Lokkevik E, Nesland JM, Anker G, et al. Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival. Breast Cancer Res. 2012;14:R117.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Juckstock J, et al. Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse—a European pooled analysis. Clin Cancer Res. 2011;17:2967–76.

    Article  PubMed  Google Scholar 

  24. Stathopoulou A, Vlachonikolis I, Mavroudis D, Perraki M, Kouroussis C, Apostolaki S, et al. Molecular detection of cytokeratin-19-positive cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic significance. J Clin Oncol. 2002;20:3404–12.

    Article  CAS  PubMed  Google Scholar 

  25. Stathopoulou A, Gizi A, Perraki M, Apostolaki S, Malamos N, Mavroudis D, et al. Real-time quantification of CK-19 mRNA-positive cells in peripheral blood of breast cancer patients using the lightcycler system. Clin Cancer Res. 2003;9:5145–51.

    CAS  PubMed  Google Scholar 

  26. Stathopoulou A, Ntoulia M, Perraki M, Apostolaki S, Mavroudis D, Malamos N, et al. A highly specific real-time RT-PCR method for the quantitative determination of CK-19 mRNA positive cells in peripheral blood of patients with operable breast cancer. Int J Cancer. 2006;119:1654–9.

    Article  CAS  PubMed  Google Scholar 

  27. Xenidis N, Perraki M, Kafousi M, Apostolaki S, Bolonaki I, Stathopoulou A, et al. Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients. J Clin Oncol. 2006;24:3756–62.

    Article  CAS  PubMed  Google Scholar 

  28. Xenidis N, Markos V, Apostolaki S, Perraki M, Pallis A, Sfakiotaki G, et al. Clinical relevance of circulating CK-19 mRNA-positive cells detected during the adjuvant tamoxifen treatment in patients with early breast cancer. Ann Oncol. 2007;18:1623–31.

    Article  CAS  PubMed  Google Scholar 

  29. Xenidis N, Ignatiadis M, Apostolaki S, Perraki M, Kalbakis K, Agelaki S, et al. Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer. J Clin Oncol. 2009;27:2177–84.

    Article  CAS  PubMed  Google Scholar 

  30. Ignatiadis M, Xenidis N, Perraki M, Apostolaki S, Politaki E, Kafousi M, et al. Different prognostic value of cytokeratin-19 mRNA positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer. J Clin Oncol. 2007;25:5194–202.

    Article  PubMed  Google Scholar 

  31. Benoy IH, Elst H, Philips M, Wuyts H, Van DP, Scharpe S, et al. Real-time RT-PCR detection of disseminated tumour cells in bone marrow has superior prognostic significance in comparison with circulating tumour cells in patients with breast cancer. Br J Cancer. 2006;94:672–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Pierga JY, Bidard FC, Mathiot C, Brain E, Delaloge S, Giachetti S, et al. Circulating tumor cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase II randomized trial. Clin Cancer Res. 2008;14:7004–10.

    Article  CAS  PubMed  Google Scholar 

  33. Saloustros E, Perraki M, Apostolaki S, Kallergi G, Xyrafas A, Kalbakis K, et al. Cytokeratin-19 mRNA-positive circulating tumor cells during follow-up of patients with operable breast cancer: prognostic relevance for late relapse. Breast Cancer Res. 2011;13:R60.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Lucci A, Hall CS, Lodhi AK, Bhattacharyya A, Anderson AE, Xiao L, et al. Circulating tumour cells in non-metastatic breast cancer: a prospective study. Lancet Oncol. 2012;13:688–95.

    Article  PubMed  Google Scholar 

  35. Banys M, Gruber I, Krawczyk N, Becker S, Kurth R, Wallwiener D, et al. Hematogenous and lymphatic tumor cell dissemination may be detected in patients diagnosed with ductal carcinoma in situ of the breast. Breast Cancer Res Treat. 2012;131:801–8.

    Article  CAS  PubMed  Google Scholar 

  36. Sanger N, Effenberger KE, Riethdorf S, Van Haasteren V, Gauwerky J, Wiegratz I, et al. Disseminated tumor cells in the bone marrow of patients with ductal carcinoma in situ. Int J Cancer. 2011;129:2522–6.

    Article  PubMed  Google Scholar 

  37. Groot KB, Rahbari NN, Buchler MW, Koch M, Weitz J. Circulating tumor cells and prognosis of patients with resectable colorectal liver metastases or widespread metastatic colorectal cancer: a meta-analysis. Ann Surg Oncol. 2013;20(7):2156–65.

    Article  Google Scholar 

  38. Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:3213–21.

    Article  PubMed  Google Scholar 

  39. Tol J, Koopman M, Miller MC, Tibbe A, Cats A, Creemers GJ, et al. Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents. Ann Oncol. 2010;21:1006–12.

    Article  CAS  PubMed  Google Scholar 

  40. Matsusaka S, Suenaga M, Mishima Y, Kuniyoshi R, Takagi K, Terui Y, et al. Circulating tumor cells as a surrogate marker for determining response to chemotherapy in Japanese patients with metastatic colorectal cancer. Cancer Sci. 2011;102:1188–92.

    Article  CAS  PubMed  Google Scholar 

  41. de Albuquerque A, Kubisch I, Stolzel U, Ernst D, Boese-Landgraf J, Breier G, et al. Prognostic and predictive value of circulating tumor cell analysis in colorectal cancer patients. J Transl Med. 2012;10:222.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Jiao LR, Apostolopoulos C, Jacob J, Szydlo R, Johnson N, Tsim N, et al. Unique localization of circulating tumor cells in patients with hepatic metastases. J Clin Oncol. 2009;27:6160–5.

    Article  PubMed  Google Scholar 

  43. Rahbari NN, Bork U, Kircher A, Nimitz T, Scholch S, Kahlert C, et al. Compartmental differences of circulating tumor cells in colorectal cancer. Ann Surg Oncol. 2012;19:2195–202.

    Article  PubMed  Google Scholar 

  44. Thorsteinsson M, Jess P. The clinical significance of circulating tumor cells in non-metastatic colorectal cancer—a review. Eur J Surg Oncol. 2011;37:459–65.

    Article  CAS  PubMed  Google Scholar 

  45. Gazzaniga P, Gianni W, Raimondi C, Gradilone A, Lo Russo G, Longo F, et al. Circulating tumor cells in high-risk nonmetastatic colorectal cancer. Tumour Biol. 2013;34(5):2507–9.

    Article  CAS  PubMed  Google Scholar 

  46. Schilling D, Todenhofer T, Hennenlotter J, Schwentner C, Fehm T, Stenzl A. Isolated, disseminated and circulating tumour cells in prostate cancer. Nature Reviews Urology 9, 448–463 (August 2012).

    Google Scholar 

  47. Danila DC, Fleisher M, Scher HI. Circulating tumor cells as biomarkers in prostate cancer. Clin Cancer Res. 2011;17:3903–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Moreno JG, O’Hara SM, Gross S, Doyle G, Fritsche H, Gomella LG, et al. Changes in circulating carcinoma cells in patients with metastatic prostate cancer correlate with disease status. Urology. 2001;58:386–92.

    Article  CAS  PubMed  Google Scholar 

  49. Danila DC, Heller G, Gignac GA, Gonzalez-Espinoza R, Anand A, Tanaka E, et al. Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer. Clin Cancer Res. 2007;13:7053–8.

    Article  CAS  PubMed  Google Scholar 

  50. de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2008;14:6302–9.

    Article  PubMed  Google Scholar 

  51. Scher HI, Jia X, de Bono JS, Fleisher M, Pienta KJ, Raghavan D, et al. Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol. 2009;10:233–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Olmos D, Arkenau HT, Ang JE, Ledaki I, Attard G, Carden CP, et al. Circulating tumour cell (CTC) counts as intermediate end points in castration-resistant prostate cancer (CRPC): a single-centre experience. Ann Oncol. 2009;20:27–33.

    Article  CAS  PubMed  Google Scholar 

  53. Helo P, Cronin AM, Danila DC, Wenske S, Gonzalez-Espinoza R, Anand A, et al. Circulating prostate tumor cells detected by reverse transcription-PCR in men with localized or castration-refractory prostate cancer: concordance with Cell Search assay and association with bone metastases and with survival. Clin Chem. 2009;55:765–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Resel FL, San Jose ML, Galante RI, Moreno SJ, Olivier GC. Prognostic significance of circulating tumor cell count in patients with metastatic hormone-sensitive prostate cancer. Urology. 2012;80:1328–32.

    Article  Google Scholar 

  55. Saad F, Pantel K. The current role of circulating tumor cells in the diagnosis and management of bone metastases in advanced prostate cancer. Future Oncol. 2012;8:321–31.

    Article  CAS  PubMed  Google Scholar 

  56. Doyen J, Alix-Panabieres C, Hofman P, Parks SK, Chamorey E, Naman H, et al. Circulating tumor cells in prostate cancer: a potential surrogate marker of survival. Crit Rev Oncol Hematol. 2012;81:241–56.

    Article  PubMed  Google Scholar 

  57. Lowes LE, Lock M, Rodrigues G, D'Souza D, Bauman G, Ahmad B, et al. Circulating tumour cells in prostate cancer patients receiving salvage radiotherapy. Clin Transl Oncol. 2012;14:150–6.

    Article  CAS  PubMed  Google Scholar 

  58. Lianidou ES, Markou A, Strati A. Molecular characterization of circulating tumor cells in breast cancer: challenges and promises for individualized cancer treatment. Cancer Metastasis Rev. 2012;31:663–71.

    Article  CAS  PubMed  Google Scholar 

  59. Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med. 2008;359:366–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Rack B, Juckstock J, Gunthner-Biller M, Andergassen U, Neugebauer J, Hepp P, et al. Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients. Arch Gynecol Obstet. 2012;285:485–92.

    Article  CAS  PubMed  Google Scholar 

  61. Bozionellou V, Mavroudis D, Perraki M, Papadopoulos S, Apostolaki S, Stathopoulos E, et al. Trastuzumab administration can effectively target chemotherapy-resistant cytokeratin-19 messenger RNA-positive tumor cells in the peripheral blood and bone marrow of patients with breast cancer. Clin Cancer Res. 2004;10:8185–94.

    Article  CAS  PubMed  Google Scholar 

  62. Meng S, Tripathy D, Shete S, Ashfaq R, Haley B, Perkins S, et al. HER-2 gene amplification can be acquired as breast cancer progresses. Proc Natl Acad Sci U S A. 2004;101:9393–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Georgoulias V, Bozionelou V, Agelaki S, Perraki M, Apostolaki S, Kallergi G, et al. Trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapy-resistant CK-19mRNA-positive circulating tumor cells: results of a randomized phase II study. Ann Oncol. 2012;23:1744–50.

    Article  CAS  PubMed  Google Scholar 

  64. Magnifico A, Albano L, Campaner S, Delia D, Castiglioni F, Gasparini P, et al. Tumor-initiating cells of HER2-positive carcinoma cell lines express the highest oncoprotein levels and are sensitive to trastuzumab. Clin Cancer Res. 2009;15:2010–21.

    Article  CAS  PubMed  Google Scholar 

  65. Ignatiadis M, Rothe F, Chaboteaux C, Durbecq V, Rouas G, Criscitiello C, et al. HER2-positive circulating tumor cells in breast cancer. PLoS One. 2011;6:e15624.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Fehm T, Muller V, Aktas B, Janni W, Schneeweiss A, Stickeler E, et al. HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial. Breast Cancer Res Treat. 2010;124:403–12.

    Article  CAS  PubMed  Google Scholar 

  67. Fehm T, Hoffmann O, Aktas B, Becker S, Solomayer EF, Wallwiener D, et al. Detection and characterization of circulating tumor cells in blood of primary breast cancer patients by RT-PCR and comparison to status of bone marrow disseminated cells. Breast Cancer Res. 2009;11:R59.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Liu M, Dixon J, Xuan J. Molecular signaling distinguishes early ER-positive breast cancer recurrences despite adjuvant tamoxifen. San Antonio Breast Cancer Symposium; 2011:Abstract S1–8.

    Google Scholar 

  69. Wicha MS, Hayes DF. Circulating tumor cells: not all detected cells are bad and not all bad cells are detected. J Clin Oncol. 2011;29:1508–11.

    Article  PubMed  Google Scholar 

  70. Thiery JP, Lim CT. Tumor dissemination: an EMT affair. Cancer Cell. 2013;23:272–3.

    Article  CAS  PubMed  Google Scholar 

  71. Aktas B, Tewes M, Fehm T, Hauch S, Kimmig R, Kasimir-Bauer S. Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res. 2009;11:R46.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Kallergi G, Papadaki MA, Politaki E, Mavroudis D, Georgoulias V, Agelaki S. Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Res. 2011;13:R59.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Kasimir-Bauer S, Hoffmann O, Wallwiener D, Kimmig R, Fehm T. Expression of stem cell and epithelial-mesenchymal transition markers in primary breast cancer patients with circulating tumor cells. Breast Cancer Res. 2012;14:R15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kallergi G, Agelaki S, Kalykaki A, Stournaras C, Mavroudis D, Georgoulias V. Phosphorylated EGFR and PI3K/Akt signaling kinases are expressed in circulating tumor cells of breast cancer patients. Breast Cancer Res. 2008;10:R80.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Kallergi G, Markomanolaki H, Giannoukaraki V, Papadaki MA, Strati A, Lianidou ES, et al. Hypoxia-inducible factor-1alpha and vascular endothelial growth factor expression in circulating tumor cells of breast cancer patients. Breast Cancer Res. 2009;11:R84.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Mostert B, Jiang Y, Sieuwerts AM, Wang H, Bolt-de VJ, Biermann K, et al. KRAS and BRAF mutation status in circulating colorectal tumor cells and their correlation with primary and metastatic tumor tissue. Int J Cancer. 2013;133:130–41.

    Article  CAS  PubMed  Google Scholar 

  77. Gasch C, Bauernhofer T, Pichler M, Langer-Freitag S, Reeh M, Seifert AM, et al. Heterogeneity of epidermal growth factor receptor status and mutations of KRAS/PIK3CA in circulating tumor cells of patients with colorectal cancer. Clin Chem. 2013;59:252–60.

    Article  CAS  PubMed  Google Scholar 

  78. Barbazan J, Alonso-Alconada L, Muinelo-Romay L, Vieito M, Abalo A, Alonso-Nocelo M, et al. Molecular characterization of circulating tumor cells in human metastatic colorectal cancer. PLoS One. 2012;7:e40476.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Yokobori T, Iinuma H, Shimamura T, Imoto S, Sugimachi K, Ishii H, et al. Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis. Cancer Res. 2013;73:2059–69.

    Article  CAS  PubMed  Google Scholar 

  80. Scher HI, Morris MJ, Larson S, Heller G. Validation and clinical utility of prostate cancer biomarkers. Nat Rev Clin Oncol. 2013;10:225–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Danila DC, Anand A, Sung CC, Heller G, Leversha MA, Cao L, et al. TMPRSS2-ERG status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate. Eur Urol. 2011;60:897–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Miyamoto DT, Lee RJ, Stott SL, Ting DT, Wittner BS, Ulman M, et al. Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer. Cancer Discov. 2012;2:995–1003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Leversha MA, Han J, Asgari Z, Danila DC, Lin O, Gonzalez-Espinoza R, et al. Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer. Clin Cancer Res. 2009;15:2091–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Darshan MS, Loftus MS, Thadani-Mulero M, Levy BP, Escuin D, Zhou XK, et al. Taxane-induced blockade to nuclear accumulation of the androgen receptor predicts clinical responses in metastatic prostate cancer. Cancer Res. 2011;71:6019–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Jiang Y, Palma JF, Agus DB, Wang Y, Gross ME. Detection of androgen receptor mutations in circulating tumor cells in castration-resistant prostate cancer. Clin Chem. 2010;56:1492–5.

    Article  PubMed  Google Scholar 

  86. Armstrong AJ, Marengo MS, Oltean S, Kemeny G, Bitting RL, Turnbull JD, et al. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res. 2011;9:997–1007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Bednarz N, Eltze E, Semjonow A, Rink M, Andreas A, Mulder L, et al. BRCA1 loss preexisting in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood. Clin Cancer Res. 2010;16:3340–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Attard G, Swennenhuis JF, Olmos D, Reid AH, Vickers E, A’Hern R, et al. Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res. 2009;69:2912–8.

    Article  CAS  PubMed  Google Scholar 

  89. Goodman Jr OB, Symanowski JT, Loudyi A, Fink LM, Ward DC, Vogelzang NJ. Circulating tumor cells as a predictive biomarker in patients with hormone-sensitive prostate cancer. Clin Genitourin Cancer. 2011;9:31–8.

    Article  PubMed  Google Scholar 

  90. Stott SL, Lee RJ, Nagrath S, Yu M, Miyamoto DT, Ulkus L, et al. Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. Sci Transl Med. 2010;2:25ra23.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Strijbos MH, Gratama JW, Schmitz PI, Rao C, Onstenk W, Doyle GV, et al. Circulating endothelial cells, circulating tumour cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel. Eur J Cancer. 2010;46:2027–35.

    Article  CAS  PubMed  Google Scholar 

  92. Coumans FA, Doggen CJ, Attard G, de Bono JS, Terstappen LW. All circulating EpCAM + CK + CD45- objects predict overall survival in castration-resistant prostate cancer. Ann Oncol. 2010;21:1851–7.

    Article  CAS  PubMed  Google Scholar 

  93. Pantel K, Alix-Panabieres C. Detection methods of circulating tumor cells. J Thorac Dis. 2012;4:446–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Lianidou ES, Markou A. Circulating tumor cells in breast cancer: detection systems, molecular characterization, and future challenges. Clin Chem. 2011;57:1242–55.

    Article  CAS  PubMed  Google Scholar 

  95. Parkinson DR, Dracopoli N, Petty BG, Compton C, Cristofanilli M, Deisseroth A, et al. Considerations in the development of circulating tumor cell technology for clinical use. J Transl Med. 2012;10:138.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Yu M, Stott S, Toner M, Maheswaran S, Haber DA. Circulating tumor cells: approaches to isolation and characterization. J Cell Biol. 2011;192:373–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Tibbe AG, Miller MC, Terstappen LW. Statistical considerations for enumeration of circulating tumor cells. Cytometry A. 2007;71:154–62.

    Article  PubMed  Google Scholar 

  98. Klein CA, Seidl S, Petat-Dutter K, Offner S, Geigl JB, Schmidt-Kittler O, et al. Combined transcriptome and genome analysis of single micrometastatic cells. Nat Biotechnol. 2002;20:387–92.

    Article  CAS  PubMed  Google Scholar 

  99. Stoecklein NH, Klein CA. Genetic disparity between primary tumours, disseminated tumour cells, and manifest metastasis. Int J Cancer. 2010;126:589–98.

    Article  CAS  PubMed  Google Scholar 

  100. Fuhrmann C, Schmidt-Kittler O, Stoecklein NH, Petat-Dutter K, Vay C, Bockler K, et al. High-resolution array comparative genomic hybridization of single micrometastatic tumor cells. Nucleic Acids Res. 2008;36:e39.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Heitzer E, Auer M, Gasch C, Pichler M, Ulz P, Hoffmann EM, et al. Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res. 2013;73(10):2965–75.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, 15771, Greece

    Evi S. Lianidou Ph.D.

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  1. Evi S. Lianidou Ph.D.
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Correspondence to Evi S. Lianidou Ph.D. .

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  1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    George M. Yousef

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Serge Jothy

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Lianidou, E.S. (2014). Circulating Tumor Cells: A Noninvasive Liquid Biopsy in Cancer. In: Yousef, G., Jothy, S. (eds) Molecular Testing in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8050-2_9

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  • DOI: https://doi.org/10.1007/978-1-4899-8050-2_9

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  • Print ISBN: 978-1-4899-8049-6

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