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Evolution of Metastatic Disease: The Need for Monitoring and Emerging Therapeutic Opportunities

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Circulating Tumor Cells

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

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Abstract

During the last few years tailored therapies have improved overall survival of patients with metastatic disease. However, iatrogenic selection pressure continues to drive the evolution of systemically spread cancer cells, resulting in the generation of aggressive and therapy-resistant tumor cells. The outcome is cancer relapse and death in the majority of patients. In early disease stages, (neo) adjuvant targeted therapies often fail for unknown reasons. Therefore, diagnostic and therapeutic strategies have to be reevaluated on the basis of an evolutionary concept of disease. This obviously implies the ability to monitor the molecular evolution of the disease. To this end, a novel diagnostic pathology for systemic cancer has to be developed that will enable precision medicine for cancer patients.

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References

  1. Gupta GP, Massague J (2006) Cancer metastasis building a framework. Cell 127:679–695

    Article  CAS  PubMed  Google Scholar 

  2. Steeg PS (2006) Tumor metastasis mechanistic insights and clinical challenges. Nat Med 12:895–904

    Article  CAS  PubMed  Google Scholar 

  3. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer the PRIME study. J Clin Oncol 28:4697–4705

    Article  CAS  PubMed  Google Scholar 

  4. Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957

    Article  CAS  PubMed  Google Scholar 

  5. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792

    Article  CAS  PubMed  Google Scholar 

  6. Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK, Ribas A (2012) Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 366:707–714

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, Smyrk TC, Sinicrope FA, Chan E, Gill S, Kahlenberg MS, Shields AF, Quesenberry JT, Webb TA, Farr GH Jr, Pockaj BA, Grothey A, Goldberg RM (2012) Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer a randomized trial. JAMA 307:1383–1393

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Goss GD, O’Callaghan C, Lorimer I, Tsao MS, Masters GA, Jett J, Edelman MJ, Lilenbaum R, Choy H, Khuri F, Pisters K, Gandara D, Kernstine K, Butts C, Noble J, Hensing TA, Rowland K, Schiller J, Ding K, Shepherd FA (2013) Gefitinib versus placebo in completely resected non-small-cell lung cancer results of the NCIC CTG BR19 study. J Clin Oncol 31:3320–3326

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194:23–28

    Article  CAS  PubMed  Google Scholar 

  10. Cairns J (1975) Mutation selection and the natural history of cancer. Nature 255:197–200

    Article  CAS  PubMed  Google Scholar 

  11. Greaves M, Maley CC (2012) Clonal evolution in cancer. Nature 481:306–313

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Heng HH, Stevens JB, Bremer SW, Liu G, Abdallah BY, Ye CJ (2011) Evolutionary mechanisms and diversity in cancer. Adv Cancer Res 112:217–253

    Article  CAS  PubMed  Google Scholar 

  13. Klein CA (2013) Selection and adaptation during metastatic cancer progression. Nature 501:365–372

    Article  CAS  PubMed  Google Scholar 

  14. Stratton MR (2011) Exploring the genomes of cancer cells progress and promise. Science 331:1553–1558

    Article  CAS  PubMed  Google Scholar 

  15. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, Varela I, Phillimore B, Begum S, McDonald NQ, Butler A, Jones D, Raine K, Latimer C, Santos CR, Nohadani M, Eklund AC, Spencer-Dene B, Clark G, Pickering L, Stamp G, Gore M, Szallasi Z, Downward J, Futreal PA, Swanton C (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892

    Article  CAS  PubMed  Google Scholar 

  16. Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, Wigler M (2011) Tumour evolution inferred by single-cell sequencing. Nature 472:90–94

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suva ML, Regev A, Bernstein BE (2014) Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science 344:1396–1401

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Klein CA, Blankenstein TJ, Schmidt-Kittler O, Petronio M, Polzer B, Stoecklein NH, Riethmuller G (2002) Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet 360:683–689

    Article  CAS  PubMed  Google Scholar 

  19. Wang Y, Waters J, Leung ML, Unruh A, Roh W, Shi X, Chen K, Scheet P, Vattathil S, Liang H, Multani A, Zhang H, Zhao R, Michor F, Meric-Bernstam F, Navin NE (2014) Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature 512:155

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN, Cancer Genome Atlas Research N (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Maley CC, Galipeau PC, Finley JC, Wongsurawat VJ, Li X, Sanchez CA, Paulson TG, Blount PL, Risques RA, Rabinovitch PS, Reid BJ (2006) Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nat Genet 38:468–473

    Article  CAS  PubMed  Google Scholar 

  22. Park SY, Gonen M, Kim HJ, Michor F, Polyak K (2010) Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. J Clin Invest 120:636–644

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Almendro V, Kim HJ, Cheng YK, Gonen M, Itzkovitz S, Argani P, van Oudenaarden A, Sukumar S, Michor F, Polyak K (2014) Genetic and phenotypic diversity in breast tumor metastases. Cancer Res 74:1338–1348

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Fidler IJ (2003) The pathogenesis of cancer metastasis the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3:453–458

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Nguyen DX, Bos PD, Massague J (2009) Metastasis from dissemination to organ-specific colonization. Nat Rev Cancer 9:274–284

    Article  CAS  PubMed  Google Scholar 

  27. Valastyan S, Weinberg RA (2011) Tumor metastasis molecular insights and evolving paradigms. Cell 147:275–292

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572

    Article  CAS  PubMed  Google Scholar 

  29. Klein G (1998) Foulds’ dangerous idea revisited the multistep development of tumors 40 years later. Adv Cancer Res 72:1–23

    Article  CAS  PubMed  Google Scholar 

  30. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    Article  CAS  PubMed  Google Scholar 

  31. Weinstein IB, Joe A (2008) Oncogene addiction. Cancer Res 68:3077–3080, discussion 3080

    Article  CAS  PubMed  Google Scholar 

  32. Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, Untch M, Smith I, Baselga J, Jackisch C, Cameron D, Mano M, Pedrini JL, Veronesi A, Mendiola C, Pluzanska A, Semiglazov V, Vrdoljak E, Eckart MJ, Shen Z, Skiadopoulos G, Procter M, Pritchard KI, Piccart-Gebhart MJ, Bell R, Herceptin Adjuvant Trial Study T (2011) Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer a 4-year follow-up of a randomised controlled trial. Lancet Oncol 12:236–244

    Article  CAS  PubMed  Google Scholar 

  33. Douillard JY, Shepherd FA, Hirsh V, Mok T, Socinski MA, Gervais R, Liao ML, Bischoff H, Reck M, Sellers MV, Watkins CL, Speake G, Armour AA, Kim ES (2010) Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer data from the randomized phase III INTEREST trial. J Clin Oncol 28:744–752

    Article  CAS  PubMed  Google Scholar 

  34. Liu D, Aguirre Ghiso J, Estrada Y, Ossowski L (2002) EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma. Cancer Cell 1:445–457

    Article  CAS  PubMed  Google Scholar 

  35. Stoecklein NH, Klein CA (2010) Genetic disparity between primary tumours, disseminated tumour cells, and manifest metastasis. Int J Cancer 126:589–598

    Article  CAS  PubMed  Google Scholar 

  36. Gow CH, Chang YL, Hsu YC, Tsai MF, Wu CT, Yu CJ, Yang CH, Lee YC, Yang PC, Shih JY (2009) Comparison of epidermal growth factor receptor mutations between primary and corresponding metastatic tumors in tyrosine kinase inhibitor-naive non-small-cell lung cancer. Ann Oncol 20:696–702

    Article  PubMed  Google Scholar 

  37. Klein CA (2009) Parallel progression of primary tumours and metastases. Nat Rev Cancer 9:302–312

    Article  CAS  PubMed  Google Scholar 

  38. Banys M, Gruber I, Krawczyk N, Becker S, Kurth R, Wallwiener D, Jakubowska J, Hoffmann J, Rothmund R, Staebler A, Fehm T (2012) Hematogenous and lymphatic tumor cell dissemination may be detected in patients diagnosed with ductal carcinoma in situ of the breast. Breast Cancer Res Treat 131:801–808

    Article  CAS  PubMed  Google Scholar 

  39. Husemann Y, Geigl JB, Schubert F, Musiani P, Meyer M, Burghart E, Forni G, Eils R, Fehm T, Riethmuller G, Klein CA (2008) Systemic spread is an early step in breast cancer. Cancer Cell 13:58–68

    Article  PubMed  Google Scholar 

  40. Sanger N, Effenberger KE, Riethdorf S, Van Haasteren V, Gauwerky J, Wiegratz I, Strebhardt K, Kaufmann M, Pantel K (2011) Disseminated tumor cells in the bone marrow of patients with ductal carcinoma in situ. Int J Cancer 129:2522–2526

    Article  PubMed  Google Scholar 

  41. Schardt JA, Meyer M, Hartmann CH, Schubert F, Schmidt-Kittler O, Fuhrmann C, Polzer B, Petronio M, Eils R, Klein CA (2005) Genomic analysis of single cytokeratin-positive cells from bone marrow reveals early mutational events in breast cancer. Cancer Cell 8:227–239

    Article  CAS  PubMed  Google Scholar 

  42. Schmidt-Kittler O, Ragg T, Daskalakis A, Granzow M, Ahr A, Blankenstein TJ, Kaufmann M, Diebold J, Arnholdt H, Muller P, Bischoff J, Harich D, Schlimok G, Riethmuller G, Eils R, Klein CA (2003) From latent disseminated cells to overt metastasis genetic analysis of systemic breast cancer progression. Proc Natl Acad Sci U S A 100:7737–7742

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Stoecklein NH, Hosch SB, Bezler M, Stern F, Hartmann CH, Vay C, Siegmund A, Scheunemann P, Schurr P, Knoefel WT, Verde PE, Reichelt U, Erbersdobler A, Grau R, Ullrich A, Izbicki JR, Klein CA (2008) Direct genetic analysis of single disseminated cancer cells for prediction of outcome and therapy selection in esophageal cancer. Cancer Cell 13:441–453

    Article  CAS  PubMed  Google Scholar 

  44. Weckermann D, Polzer B, Ragg T, Blana A, Schlimok G, Arnholdt H, Bertz S, Harzmann R, Klein CA (2009) Perioperative activation of disseminated tumor cells in bone marrow of patients with prostate cancer. J Clin Oncol 27:1549–1556

    Article  PubMed  Google Scholar 

  45. Klein CA (2011) Framework models of tumor dormancy from patient-derived observations. Curr Opin Genet Dev 21:42–49

    Article  CAS  PubMed  Google Scholar 

  46. Burrell RA, Swanton C (2014) Tumour heterogeneity and the evolution of polyclonal drug resistance. Mol Oncol 8:1095

    Article  CAS  PubMed  Google Scholar 

  47. Ashworth TR (1869) A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Aust Med J 14:146–147

    Google Scholar 

  48. Fischer JC, Niederacher D, Topp SA, Honisch E, Schumacher S, Schmitz N, Zacarias Fohrding L, Vay C, Hoffmann I, Kasprowicz NS, Hepp PG, Mohrmann S, Nitz U, Stresemann A, Krahn T, Henze T, Griebsch E, Raba K, Rox JM, Wenzel F, Sproll C, Janni W, Fehm T, Klein CA, Knoefel WT, Stoecklein NH (2013) Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients. Proc Natl Acad Sci U S A 110:16580–16585

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Miller MC, Doyle GV, Terstappen LW (2010) Significance of circulating tumor cells detected by the cell search system in patients with metastatic breast colorectal and prostate cancer. J Oncol 2010:617421

    Article  PubMed Central  PubMed  Google Scholar 

  50. Schlimok G, Funke I, Holzmann B, Göttlinger G, Schmidt G, Häuser H, Swierkot S, Warnecke HH, Schneider B, Koprowski H (1987) Micrometastatic cancer cells in bone marrow in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. Proc Natl Acad Sci U S A 84:8672–8676

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Tibbe AG, Miller MC, Terstappen LW (2007) Statistical considerations for enumeration of circulating tumor cells. Cytometry A 71:154–162

    Article  PubMed  Google Scholar 

  52. Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW (2004) Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res 10:6897–6904

    Article  PubMed  Google Scholar 

  53. Pantel K, Deneve E, Nocca D, Coffy A, Vendrell JP, Maudelonde T, Riethdorf S, Alix-Panabieres C (2012) Circulating epithelial cells in patients with benign colon diseases. Clin Chem 58:936–940

    Article  CAS  PubMed  Google Scholar 

  54. Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, Picus J, Morse M, Mitchell E, Miller MC, Doyle GV, Tissing H, Terstappen LW, Meropol NJ (2008) Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26:3213–3221

    Article  PubMed  Google Scholar 

  55. Cristofanilli M, Hayes DF, Budd GT, Ellis MJ, Stopeck A, Reuben JM, Doyle GV, Matera J, Allard WJ, Miller MC, Fritsche HA, Hortobagyi GN, Terstappen LW (2005) Circulating tumor cells a novel prognostic factor for newly diagnosed metastatic breast cancer. J Clin Oncol 23:1420–1430

    Article  PubMed  Google Scholar 

  56. de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H, Doyle GV, Terstappen LW, Pienta KJ, Raghavan D (2008) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14:6302–6309

    Article  PubMed  Google Scholar 

  57. Rack B, Schindlbeck C, Juckstock J, Andergassen U, Hepp P, Zwingers T, Friedl TW, Lorenz R, Tesch H, Fasching PA, Fehm T, Schneeweiss A, Lichtenegger W, Beckmann MW, Friese K, Pantel K, Janni W, Group SS (2014) Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst 106:dju066

    Article  PubMed Central  PubMed  Google Scholar 

  58. Klein CA (2003) The systemic progression of human cancer a focus on the individual disseminated cancer cell--the unit of selection. Adv Cancer Res 89:35–67

    Article  CAS  PubMed  Google Scholar 

  59. Riethdorf S, Pantel K (2009) Clinical relevance and current challenges of research on disseminating tumor cells in cancer patients. Breast Cancer Res 11(Suppl 3):S10

    Article  PubMed Central  PubMed  Google Scholar 

  60. Fehm T, Braun S, Muller V, Janni W, Gebauer G, Marth C, Schindlbeck C, Wallwiener D, Borgen E, Naume B, Pantel K, Solomayer E (2006) A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation. Cancer 107:885–892

    Article  PubMed  Google Scholar 

  61. Riethdorf S, Wikman H, Pantel K (2008) Review: biological relevance of disseminated tumor cells in cancer patients. Int J Cancer 123:1991–2006

    Article  CAS  PubMed  Google Scholar 

  62. Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Juckstock J, Borgen E, Rack B, Braun S, Sommer H, Solomayer E, Pantel K, Nesland J, Friese K, Naume B (2011) 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 17:2967–2976

    Article  PubMed  Google Scholar 

  63. Banys M, Solomayer EF, Gebauer G, Janni W, Krawczyk N, Lueck HJ, Becker S, Huober J, Kraemer B, Wackwitz B, Hirnle P, Wallwiener D, Fehm T (2013) Influence of zoledronic acid on disseminated tumor cells in bone marrow and survival results of a prospective clinical trial. BMC Cancer 13:480

    Article  PubMed Central  PubMed  Google Scholar 

  64. Synnestvedt M, Borgen E, Wist E, Wiedswang G, Weyde K, Risberg T, Kersten C, Mjaaland I, Vindi L, Schirmer C, Nesland JM, Naume B (2012) 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 12:616

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Kubuschok B, Passlick B, Izbicki JR, Thetter O, Pantel K (1999) Disseminated tumor cells in lymph nodes as a determinant for survival in surgically resected non-small-cell lung cancer. J Clin Oncol 17:19–24

    CAS  PubMed  Google Scholar 

  66. Ulmer A, Dietz K, Hodak I, Polzer B, Scheitler S, Yildiz M, Czyz Z, Lehnert P, Fehm T, Hafner C, Schanz S, Rocken M, Garbe C, Breuninger H, Fierlbeck G, Klein CA (2014) Quantitative measurement of melanoma spread in sentinel lymph nodes and survival. PLoS Med 11:e1001604

    Article  PubMed Central  PubMed  Google Scholar 

  67. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206

    Article  PubMed Central  PubMed  Google Scholar 

  68. Muller V, Riethdorf S, Rack B, Janni W, Fasching PA, Solomayer E, Aktas B, Kasimir-Bauer S, Pantel K, Fehm T, group Ds (2012) 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 14:R118

    Article  PubMed Central  PubMed  Google Scholar 

  69. Riethdorf S, Muller V, Zhang L, Rau T, Loibl S, Komor M, Roller M, Huober J, Fehm T, Schrader I, Hilfrich J, Holms F, Tesch H, Eidtmann H, Untch M, von Minckwitz G, Pantel K (2010) Detection and HER2 expression of circulating tumor cells prospective monitoring in breast cancer patients treated in the neoadjuvant GeparQuattro trial. Clin Cancer Res 16:2634–2645

    Article  CAS  PubMed  Google Scholar 

  70. Fehm T, Muller V, Aktas B, Janni W, Schneeweiss A, Stickeler E, Lattrich C, Lohberg CR, Solomayer E, Rack B, Riethdorf S, Klein C, Schindlbeck C, Brocker K, Kasimir-Bauer S, Wallwiener D, Pantel K (2010) HER2 status of circulating tumor cells in patients with metastatic breast cancer a prospective, multicenter trial. Breast Cancer Res Treat 124:403–412

    Article  CAS  PubMed  Google Scholar 

  71. Lankiewicz S, Rother E, Zimmermann S, Hollmann C, Korangy F, Greten TF (2008) Tumour-associated transcripts and EGFR deletion variants in colorectal cancer in primary tumour, metastases and circulating tumour cells. Cell Oncol 30:463–471

    PubMed Central  CAS  PubMed  Google Scholar 

  72. Pestrin M, Bessi S, Puglisi F, Minisini AM, Masci G, Battelli N, Ravaioli A, Gianni L, Di Marsico R, Tondini C, Gori S, Coombes CR, Stebbing J, Biganzoli L, Buyse M, Di Leo A (2012) Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study. Breast Cancer Res Treat 134:283–289

    Article  CAS  PubMed  Google Scholar 

  73. Stebbing J, Payne R, Reise J, Frampton AE, Avery M, Woodley L, Di Leo A, Pestrin M, Krell J, Coombes RC (2013) The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells a proof-of-concept study. PLoS One 8:e62543

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, Digumarthy S, Muzikansky A, Irimia D, Settleman J, Tompkins RG, Lynch TJ, Toner M, Haber DA (2008) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359:366–377

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, Gursky A, Siddiqui J, Tomlins SA, Roychowdhury S, Pienta KJ, Kim SY, Roberts JS, Rae JM, Van Poznak CH, Hayes DF, Chugh R, Kunju LP, Talpaz M, Schott AF, Chinnaiyan AM (2013) Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet 45:1446–1451

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Yu M, Bardia A, Aceto N, Bersani F, Madden MW, Donaldson MC, Desai R, Zhu H, Comaills V, Zheng Z, Wittner BS, Stojanov P, Brachtel E, Sgroi D, Kapur R, Shioda T, Ting DT, Ramaswamy S, Getz G, Iafrate AJ, Benes C, Toner M, Maheswaran S, Haber DA (2014) Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science 345:216–220

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, Moliterni A, Vazquez F, Byakhov MJ, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Magazzu D, Heinzmann D, Steinseifer J, Valagussa P, Baselga J (2014) Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH) follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol 15:640–647

    Article  CAS  PubMed  Google Scholar 

  78. Krishnamurthy S, Bischoff F, Ann Mayer J, Wong K, Pham T, Kuerer H, Lodhi A, Bhattacharyya A, Hall C, Lucci A (2013) Discordance in HER2 gene amplification in circulating and disseminated tumor cells in patients with operable breast cancer. Cancer Med 2:226–233

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  79. Paik S, Kim C, Wolmark N (2008) HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med 358:1409–1411

    Article  CAS  PubMed  Google Scholar 

  80. Perez EA, Reinholz MM, Hillman DW, Tenner KS, Schroeder MJ, Davidson NE, Martino S, Sledge GW, Harris LN, Gralow JR, Dueck AC, Ketterling RP, Ingle JN, Lingle WL, Kaufman PA, Visscher DW, Jenkins RB (2010) HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol 28:4307–4315

    Article  PubMed Central  PubMed  Google Scholar 

  81. Korkaya H, Paulson A, Iovino F, Wicha MS (2008) HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion. Oncogene 27:6120–6130

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Ithimakin S, Day KC, Malik F, Zen Q, Dawsey SJ, Bersano-Begey TF, Quraishi AA, Ignatoski KW, Daignault S, Davis A, Hall CL, Palanisamy N, Heath AN, Tawakkol N, Luther TK, Clouthier SG, Chadwick WA, Day ML, Kleer CG, Thomas DG, Hayes DF, Korkaya H, Wicha MS (2013) HER2 drives luminal breast cancer stem cells in the absence of HER2 amplification implications for efficacy of adjuvant trastuzumab. Cancer Res 73:1635–1646

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Dawson SJ, Tsui DW, Murtaza M, Biggs H, Rueda OM, Chin SF, Dunning MJ, Gale D, Forshew T, Mahler-Araujo B, Rajan S, Humphray S, Becq J, Halsall D, Wallis M, Bentley D, Caldas C, Rosenfeld N (2013) Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 368:1199–1209

    Article  CAS  PubMed  Google Scholar 

  84. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih IM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6:224ra24

    Article  PubMed Central  PubMed  Google Scholar 

  85. Araki T, Yamamoto A, Yamada M (1987) Accurate determination of DNA content in single cell nuclei stained with Hoechst 33258 fluorochrome at high salt concentration. Histochemistry 87:331–338

    Article  CAS  PubMed  Google Scholar 

  86. Telenius H, Carter NP, Bebb CE, Nordenskjold M, Ponder BA, Tunnacliffe A (1992) Degenerate oligonucleotide-primed PCR general amplification of target DNA by a single degenerate primer. Genomics 13:718–725

    Article  CAS  PubMed  Google Scholar 

  87. Zhang L, Cui X, Schmitt K, Hubert R, Navidi W, Arnheim N (1992) Whole genome amplification from a single cell implications for genetic analysis. Proc Natl Acad Sci U S A 89:5847–5851

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Klein CA, Schmidt-Kittler O, Schardt JA, Pantel K, Speicher MR, Riethmuller G (1999) Comparative genomic hybridization, loss of heterozygosity, and DNA sequence analysis of single cells. Proc Natl Acad Sci U S A 96:4494–4499

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. Blanco L, Bernad A, Lazaro JM, Martin G, Garmendia C, Salas M (1989) Highly efficient DNA synthesis by the phage phi 29 DNA polymerase. Symmetrical mode of DNA replication. J Biol Chem 264:8935–8940

    CAS  PubMed  Google Scholar 

  90. Dean FB, Nelson JR, Giesler TL, Lasken RS (2001) Rapid amplification of plasmid and phage DNA using Phi 29 DNA polymerase and multiply-primed rolling circle amplification. Genome Res 11:1095–1099

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Zong C, Lu S, Chapman AR, Xie XS (2012) Genome-wide detection of single-nucleotide and copy-number variations of a single human cell. Science 338:1622–1626

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  92. Mehes G, Witt A, Kubista E, Ambros PF (2001) Circulating breast cancer cells are frequently apoptotic. Am J Pathol 159:17–20

    Google Scholar 

  93. Moller EK, Kumar P, Voet T, Peterson A, Van Loo P, Mathiesen RR, Fjelldal R, Grundstad J, Borgen E, Baumbusch LO, Naume B, Borresen-Dale AL, White KP, Nord S, Kristensen VN (2013) Next-generation sequencing of disseminated tumor cells. Front Oncol 3:320

    Article  PubMed Central  PubMed  Google Scholar 

  94. Binder V, Bartenhagen C, Okpanyi V, Gombert M, Moehlendick B, Behrens B, Klein HU, Rieder H, Ida Krell PF, Dugas M, Stoecklein NH, Borkhardt A (2014) A new workflow for whole-genome sequencing of single human cells. Hum Mutat 35:1260–1270

    Article  CAS  PubMed  Google Scholar 

  95. Voet T, Kumar P, Van Loo P, Cooke SL, Marshall J, Lin ML, Zamani Esteki M, Van der Aa N, Mateiu L, McBride DJ, Bignell GR, McLaren S, Teague J, Butler A, Raine K, Stebbings LA, Quail MA, D’Hooghe T, Moreau Y, Futreal PA, Stratton MR, Vermeesch JR, Campbell PJ (2013) Single-cell paired-end genome sequencing reveals structural variation per cell cycle. Nucleic Acids Res 41:6119–6138

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Handyside AH, Robinson MD, Simpson RJ, Omar MB, Shaw MA, Grudzinskas JG, Rutherford A (2004) Isothermal whole genome amplification from single and small numbers of cells a new era for preimplantation genetic diagnosis of inherited disease. Mol Hum Reprod 10:767–772

    Article  CAS  PubMed  Google Scholar 

  97. Hellani A, Coskun S, Benkhalifa M, Tbakhi A, Sakati N, Al-Odaib A, Ozand P (2004) Multiple displacement amplification on single cell and possible PGD applications. Mol Hum Reprod 10:847–852

    Article  CAS  PubMed  Google Scholar 

  98. Daley T, Smith AD (2014) Modeling genome coverage in single cell sequencing. Bioinformatics 30:3159

    Article  PubMed Central  PubMed  Google Scholar 

  99. Ni X, Zhuo M, Su Z, Duan J, Gao Y, Wang Z, Zong C, Bai H, Chapman AR, Zhao J, Xu L, An T, Ma Q, Wang Y, Wu M, Sun Y, Wang S, Li Z, Yang X, Yong J, Su XD, Lu Y, Bai F, Xie XS, Wang J (2013) Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proc Natl Acad Sci U S A 110:21083–21088

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  100. Polzer B, Medoro G, Pasch S, Fontana F, Zorzino L, Pestka A, Andergassen U, Meier-Stiegen F, Czyz ZT, Alberter B, Treitschke S, Schamberger T, Sergio M, Bregola G, Doffini A, Gianni S, Calanca A, Signorini G, Bolognesi C, Hartmann A, Fasching PA, Sandri MT, Rack B, Fehm R, Giorgini G, Manaresi N, Klein CA. Molecular profiling of single circulating tumor cells with diagnostic intention. EMBO Mol Med 2014; 6(11):1371–86.

    Google Scholar 

  101. Smerage JB, Barlow WE, Hortobagyi GN, Winer EP, Leyland-Jones B, Srkalovic G, Tejwani S, Schott AF, O’Rourke MA, Lew DL, Doyle GV, Gralow JR, Livingston RB, Hayes DF (2014) Circulating tumor cells and response to chemotherapy in metastatic breast cancer SWOG S0500. J Clin Oncol 32:3483

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany

    Bernhard Polzer M.D.

  2. Experimental Medicine and Therapy Research, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany

    Christoph A. Klein M.D.

  3. Fraunhofer Project Group “Personalized Tumor Therapy” ITEM Regensburg, Josef-Engert Str. 9, 93053, Regensburg, Germany

    Christoph A. Klein M.D.

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  1. Bernhard Polzer M.D.
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Correspondence to Christoph A. Klein M.D. .

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  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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Polzer, B., Klein, C.A. (2016). Evolution of Metastatic Disease: The Need for Monitoring and Emerging Therapeutic Opportunities. 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_14

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