Circulating tumor cells: Advances in isolation and analysis, and challenges for clinical applications

Aktas, 2011, Molecular profiling and prognostic relevance of circulating tumor cells in the blood of ovarian cancer patients at primary diagnosis and after platinum-based chemotherapy, Int J Gynecol Cancer, 21, 822, 10.1097/IGC.0b013e318216cb91 Aktas, 2011, Comparison of estrogen and progesterone receptor status of circulating tumor cells and the primary tumor in metastatic breast cancer patients, Gynecol Oncol, 122, 356, 10.1016/j.ygyno.2011.04.039 Aktas, 2009, Stem cell and epithelial–mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients, Breast Cancer Res, 11, R46, 10.1186/bcr2333 Alix-Panabières, 2005, Characterization and enumeration of cells secreting tumor markers in the peripheral blood of breast cancer patients, J Immunol Methods, 299, 177, 10.1016/j.jim.2005.02.007 Alix-Panabières, 2013, Circulating tumor cells: liquid biopsy of cancer, Clin Chem, 59, 110, 10.1373/clinchem.2012.194258 Alix-Panabieres, 2007, Detection and characterization of putative metastatic precursor cells in cancer patients, Clin Chem, 53, 537, 10.1373/clinchem.2006.079509 Alix-Panabieres, 2009, Full-length cytokeratin-19 is released by human tumor cells: a potential role in metastatic progression of breast cancer, Breast Cancer Res, 11, R39, 10.1186/bcr2326 Allard, 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, 10.1158/1078-0432.CCR-04-0378 Andreopoulou, 2012, Comparison of assay methods for detection of circulating tumor cells in metastatic breast cancer: AdnaGen AdnaTest BreastCancer Select/Detect versus Veridex Cell Search system, Int J Cancer, 130, 1590, 10.1002/ijc.26111 Armstrong, 2011, Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers, Mol Cancer Res, 9, 997, 10.1158/1541-7786.MCR-10-0490 Ashworth, 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 Attard, 2009, Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer, Cancer Res, 69, 2912, 10.1158/0008-5472.CAN-08-3667 Baccelli, 2013, Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay, Nat Biotechnol, 31, 539, 10.1038/nbt.2576 Balic, 2005, Comparison of two methods for enumerating circulating tumor cells in carcinoma patients, Cytometry B Clin Cytom, 68B, 25, 10.1002/cyto.b.20065 Becker, 1994, The removal of human leukaemia cells from blood using interdigitated microelectrodes, J Phys D Appl Phys, 27, 2659, 10.1088/0022-3727/27/12/030 Becker, 1995, Separation of human breast cancer cells from blood by differential dielectric affinity, Proc Natl Acad Sci U S A, 92, 860, 10.1073/pnas.92.3.860 Bhagat, 2011, Pinched flow coupled shear-modulated inertial microfluidics for high-throughput rare blood cell separation, Lab Chip, 11, 1870, 10.1039/c0lc00633e Budd, 2006, Circulating tumor cells versus imaging—predicting overall survival in metastatic breast cancer, Clin Cancer Res, 12, 6403, 10.1158/1078-0432.CCR-05-1769 Carey, 1976, Carcinocythemia (carcinoma cell leukemia): an acute leukemia-like picture due to metastatic carcinoma cells, Am J Med, 60, 273, 10.1016/0002-9343(76)90437-X Chen, 2012, Single‐cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT‐related genes in metastatic prostate cancer, Prostate, 73, 813, 10.1002/pros.22625 Cho, 2012, Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors, Phys Biol, 9, 016001, 10.1088/1478-3975/9/1/016001 Cohen, 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, 10.1200/JCO.2007.15.8923 Cohen, 2009, Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer, Ann Oncol, 20, 1223, 10.1093/annonc/mdn786 Cristofanilli, 2004, Circulating tumor cells, disease progression, and survival in metastatic breast cancer, N Engl J Med, 351, 781, 10.1056/NEJMoa040766 Cristofanilli, 2005, Circulating tumor cells: a novel prognostic factor for newly diagnosed metastatic breast cancer, J Clin Oncol, 23, 1420, 10.1200/JCO.2005.08.140 Danila, 2011, 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, 60, 897, 10.1016/j.eururo.2011.07.011 Danila, 2011, Circulating tumor cells as biomarkers in prostate cancer, Clin Cancer Res, 17, 3903, 10.1158/1078-0432.CCR-10-2650 Danila, 2007, Circulating tumor cell number and prognosis in progressive castration-resistant prostate cancer, Clin Cancer Res, 13, 7053, 10.1158/1078-0432.CCR-07-1506 Danila, 2010, Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer, J Clin Oncol, 28, 1496, 10.1200/JCO.2009.25.9259 Danila, 2011, Circulating tumors cells as biomarkers: progress toward biomarker qualification, Cancer J, 17, 438, 10.1097/PPO.0b013e31823e69ac Dawson, 2013, Analysis of circulating tumor DNA to monitor metastatic breast cancer, N Engl J Med, 368, 1199, 10.1056/NEJMoa1213261 de Bono, 2011, Abiraterone and increased survival in metastatic prostate cancer, N Engl J Med, 364, 1995, 10.1056/NEJMoa1014618 de Bono, 2008, Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer, Clin Cancer Res, 14, 6302, 10.1158/1078-0432.CCR-08-0872 De Giorgi, 2010, Application of a filtration-and isolation-by-size technique for the detection of circulating tumor cells in cutaneous melanoma, J Invest Dermatol, 130, 2440, 10.1038/jid.2010.141 Devriese, 2011, Circulating tumor cells as pharmacodynamic biomarker in early clinical oncological trials, Cancer Treat Rev, 37, 579, 10.1016/j.ctrv.2011.04.006 Diaz, 2012, The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers, Nature, 486, 537, 10.1038/nature11219 Diehl, 2008, Circulating mutant DNA to assess tumor dynamics, Nat Med, 14, 985, 10.1038/nm.1789 Earhart, 2013, Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips, Lab Chip Farace, 2011, A direct comparison of Cell Search and ISET for circulating tumour-cell detection in patients with metastatic carcinomas, Br J Cancer, 105, 847, 10.1038/bjc.2011.294 Fehm, 2007, Determination of HER2 status using both serum HER2 levels and circulating tumor cells in patients with recurrent breast cancer whose primary tumor was HER2 negative or of unknown HER2 status, Breast Cancer Res, 9, 10.1186/bcr1783 Fehm, 2009, 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, 11, R59, 10.1186/bcr2349 Fehm, 2010, HER2 status of circulating tumor cells in patients with metastatic breast cancer: a prospective, multicenter trial, Breast Cancer Res Treat, 124, 403, 10.1007/s10549-010-1163-x Fischer, 2013, Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients, Proc Natl Acad Sci U S A, 41, 16580, 10.1073/pnas.1313594110 Forshew, 2012, Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA, Sci Transl Med, 4, 136ra168, 10.1126/scitranslmed.3003726 Gallivan, 1984, Carcinocythemia (carcinoma cell leukemia). Report of two cases with English literature review, Cancer, 53, 1100, 10.1002/1097-0142(19840301)53:5<1100::AID-CNCR2820530514>3.0.CO;2-K Gasch, 2013, Heterogeneity of epidermal growth factor receptor status and mutations of KRAS/PIK3CA in circulating tumor cells of patients with colorectal cancer, Clin Chem, 59, 252, 10.1373/clinchem.2012.188557 Ghossein, 1997, Prognostic significance of detection of prostate-specific antigen transcripts in the peripheral blood of patients with metastatic androgen-independent prostatic carcinoma, Urology, 50, 100, 10.1016/S0090-4295(97)00127-1 Gleghorn, 2010, Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential immunocapture (GEDI) and a prostate-specific antibody, Lab Chip, 10, 27, 10.1039/B917959C Grasso, 2012, The mutational landscape of lethal castration-resistant prostate cancer, Nature, 487, 239, 10.1038/nature11125 Gupta, 2012, ApoStream(™), a new dielectrophoretic device for antibody independent isolation and recovery of viable cancer cells from blood, Biomicrofluidics, 6, 24133, 10.1063/1.4731647 Hanahan, 2011, Hallmarks of cancer: the next generation, Cell, 144, 646, 10.1016/j.cell.2011.02.013 Harris, 2007, American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer, J Clin Oncol, 25, 5287, 10.1200/JCO.2007.14.2364 Hayes, 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, 4218, 10.1158/1078-0432.CCR-05-2821 He, 2008, Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor‐specific fluorescent ligands, Int J Cancer, 123, 1968, 10.1002/ijc.23717 Heitzer, 2013, Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing, Cancer Res, 73, 2965, 10.1158/0008-5472.CAN-12-4140 Helo, 2009, 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, 55, 765, 10.1373/clinchem.2008.117952 Hofman, 2011, Preoperative circulating tumor cell detection using the isolation by size of epithelial tumor cell method for patients with lung cancer is a new prognostic biomarker, Clin Cancer Res, 17, 827, 10.1158/1078-0432.CCR-10-0445 Hofman, 2011, Cytopathologic detection of circulating tumor cells using the isolation by size of epithelial tumor cell method promises and pitfalls, Am J Clin Pathol, 135, 146, 10.1309/AJCP9X8OZBEIQVVI Hosokawa, 2010, Size-selective microcavity array for rapid and efficient detection of circulating tumor cells, Anal Chem, 82, 6629, 10.1021/ac101222x Hosokawa, 2013, Size-based isolation of circulating tumor cells in lung cancer patients using a microcavity array system, PLoS One, 8, e67466, 10.1371/journal.pone.0067466 Hou, 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, 525, 10.1200/JCO.2010.33.3716 Hou, 2013, Isolation and retrieval of circulating tumor cells using centrifugal forces, Sci Rep, 3, 1259, 10.1038/srep01259 Huang, 1997, Introducing dielectrophoresis as a new force field for field-flow fractionation, Biophys J, 73, 1118, 10.1016/S0006-3495(97)78144-X Hughes, 2012, Microtube device for selectin-mediated capture of viable circulating tumor cells from blood, Clin Chem, 58, 846, 10.1373/clinchem.2011.176669 Hur, 2011, High-throughput size-based rare cell enrichment using microscale vortices, Biomicrofluidics, 5, 10.1063/1.3576780 Ignatiadis, 2011, HER2-positive circulating tumor cells in breast cancer, PLoS One, 6, e15624, 10.1371/journal.pone.0015624 Iinuma, 2011, Clinical significance of circulating tumor cells, including cancer stem-like cells, in peripheral blood for recurrence and prognosis in patients with Dukes’ stage B and C colorectal cancer, J Clin Oncol, 29, 1547, 10.1200/JCO.2010.30.5151 Issadore, 2012, Ultrasensitive clinical enumeration of rare cells ex vivo using a micro-hall detector, Sci Transl Med, 4, 141ra192, 10.1126/scitranslmed.3003747 Jiang, 2010, Detection of androgen receptor mutations in circulating tumor cells in castration-resistant prostate cancer, Clin Chem, 56, 1492, 10.1373/clinchem.2010.143297 Kallergi, 2011, Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients, Breast Cancer Res, 13, R59, 10.1186/bcr2896 Kasimir-Bauer, 2012, Expression of stem cell and epithelial–mesenchymal transition markers in primary breast cancer patients with circulating tumor cells, Breast Cancer Res, 14, R15, 10.1186/bcr3099 Kirby, 2012, Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device, PLoS One, 7, e35976, 10.1371/journal.pone.0035976 Krebs, 2011, Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer, J Clin Oncol, 29, 1556, 10.1200/JCO.2010.28.7045 Krivacic, 2004, A rare-cell detector for cancer, Proc Natl Acad Sci U S A, 101, 10501, 10.1073/pnas.0404036101 Lacy, 1998, Port site metastases and recurrence after laparoscopic colectomy, Surg Endosc, 12, 1039, 10.1007/s004649900776 Lara, 2004, Enrichment of rare cancer cells through depletion of normal cells using density and flow-through, immunomagnetic cell separation, Exp Hematol, 32, 891, 10.1016/j.exphem.2004.07.007 Lazar, 2012, Cytometric comparisons between circulating tumor cells from prostate cancer patients and the prostate-tumor-derived LNCaP cell line, Phys Biol, 9, 016002, 10.1088/1478-3975/9/1/016002 Lecharpentier, 2011, Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer, Br J Cancer, 105, 1338, 10.1038/bjc.2011.405 Leversha, 2009, Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer, Clin Cancer Res, 15, 2091, 10.1158/1078-0432.CCR-08-2036 Liedtke, 2009, Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer, Ann Oncol, 20, 1953, 10.1093/annonc/mdp263 Lim, 2012, Microsieve lab-chip device for rapid enumeration and fluorescence in situ hybridization of circulating tumor cells, Lab Chip, 12, 4388, 10.1039/c2lc20750h Lin, 2010, Portable filter-based microdevice for detection and characterization of circulating tumor cells, Clin Cancer Res, 16, 5011, 10.1158/1078-0432.CCR-10-1105 Liu, 2012, ROCK inhibitor and feeder cells induce the conditional reprogramming of epithelial cells, Am J Pathol, 180, 599, 10.1016/j.ajpath.2011.10.036 Liu, 2009, Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer, J Clin Oncol, 27, 5153, 10.1200/JCO.2008.20.6664 Maheswaran, 2008, Detection of mutations in EGFR in circulating lung-cancer cells, N Engl J Med, 359, 366, 10.1056/NEJMoa0800668 Mao, 2008, Detection of TMPRSS2: ERG fusion gene in circulating prostate cancer cells, Asian J Androl, 10, 467, 10.1111/j.1745-7262.2008.00401.x Markou, 2011, Molecular characterization of circulating tumor cells in breast cancer by a liquid bead array hybridization assay, Clin Chem, 57, 421, 10.1373/clinchem.2010.154328 Marrinucci, 2012, Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers, Phys Biol, 9, 016003, 10.1088/1478-3975/9/1/016003 Meng, 2004, HER-2 gene amplification can be acquired as breast cancer progresses, Proc Natl Acad Sci U S A, 101, 9393, 10.1073/pnas.0402993101 Misale, 2012, Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer, Nature, 486, 532, 10.1038/nature11156 Miyamoto, 2012, Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer, Cancer Discov, 2, 995, 10.1158/2159-8290.CD-12-0222 Muller, 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, 3678, 10.1158/1078-0432.CCR-04-2469 Murtaza, 2013, Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA, Nature, 497, 108, 10.1038/nature12065 Myerowitz, 1977, Carcinocythemia (carcinoma cell leukemia) due to metastatic carcinoma of the breast. Report of a case, Cancer, 40, 3107, 10.1002/1097-0142(197712)40:6<3107::AID-CNCR2820400653>3.0.CO;2-5 Nagrath, 2007, Isolation of rare circulating tumour cells in cancer patients by microchip technology, Nature, 450, 1235, 10.1038/nature06385 Nieva, 2012, High-definition imaging of circulating tumor cells and associated cellular events in non-small cell lung cancer patients: a longitudinal analysis, Phys Biol, 9, 016004, 10.1088/1478-3975/9/1/016004 Ozkumur, 2013, Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells, Sci Transl Med, 5, 179ra147, 10.1126/scitranslmed.3005616 Pachmann, 2008, Monitoring the response of circulating epithelial tumor cells to adjuvant chemotherapy in breast cancer allows detection of patients at risk of early relapse, J Clin Oncol, 26, 1208, 10.1200/JCO.2007.13.6523 Pailler, 2013, Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer, J Clin Oncol, 31, 2273, 10.1200/JCO.2012.44.5932 Parkinson, 2012, Considerations in the development of circulating tumor cell technology for clinical use, J Transl Med, 10, 138, 10.1186/1479-5876-10-138 Pestrin, 2009, Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients, Breast Cancer Res Treat, 118, 523, 10.1007/s10549-009-0461-7 Phillips, 2012, Optical quantification of cellular mass, volume, and density of circulating tumor cells identified in an ovarian cancer patient, Front Oncol, 2, 72 Powell, 2012, Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines, PLoS One, 7, e33788, 10.1371/journal.pone.0033788 Punnoose, 2010, Molecular biomarker analyses using circulating tumor cells, PLoS One, 5, e12517, 10.1371/journal.pone.0012517 Rathkopf, 2013, Androgen receptor antagonists in castration-resistant prostate cancer, Cancer J, 19, 43, 10.1097/PPO.0b013e318282635a Reid, 2010, Significant and sustained antitumor activity in post-docetaxel, castration-resistant prostate cancer with the CYP17 inhibitor abiraterone acetate, J Clin Oncol, 28, 1489, 10.1200/JCO.2009.24.6819 Riethdorf, 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, 10.1158/1078-0432.CCR-09-2042 Rosenberg, 2002, Comparison of two density gradient centrifugation systems for the enrichment of disseminated tumor cells in blood, Cytometry, 49, 150, 10.1002/cyto.10161 Saucedo-Zeni, 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, 1241 Scher, 2009, Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data, Lancet Oncol, 10, 233, 10.1016/S1470-2045(08)70340-1 Scher, 2013, Validation and clinical utility of prostate cancer biomarkers, Nat Rev Clin Oncol, 10, 225, 10.1038/nrclinonc.2013.30 Shaffer, 2007, Circulating tumor cell analysis in patients with progressive castration-resistant prostate cancer, Clin Cancer Res, 13, 2023, 10.1158/1078-0432.CCR-06-2701 Shim, 2013, Dielectrophoresis has broad applicability to marker-free isolation of tumor cells from blood by microfluidic systems, Biomicrofluidics, 7, 011808, 10.1063/1.4774307 Sieuwerts, 2009, Anti-epithelial cell adhesion molecule antibodies and the detection of circulati ng normal-like breast tumor cells, J Natl Cancer Inst, 101, 61, 10.1093/jnci/djn419 Sieuwerts, 2011, mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients, Clin Cancer Res, 17, 3600, 10.1158/1078-0432.CCR-11-0255 Simmons, 2009, Does confirmatory tumor biopsy alter the management of breast cancer patients with distant metastases?, Ann Oncol, 20, 1499, 10.1093/annonc/mdp028 Sollier, 2013, Size-selective collection of circulating tumor cells using vortex technology, Lab Chip Steeg, 2003, Metastasis suppressors alter the signal transduction of cancer cells, Nat Rev Cancer, 3, 55, 10.1038/nrc967 Stott, 2010, Isolation of circulating tumor cells using a microvortex-generating herringbone-chip, Proc Natl Acad Sci U S A, 107, 18392, 10.1073/pnas.1012539107 Stott, 2010, Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer, Sci Transl Med, 2, 25ra23, 10.1126/scitranslmed.3000403 Strati, 2013, Comparison of three molecular assays for the detection and molecular characterization of circulating tumor cells in breast cancer, Breast Cancer Res, 15, R20, 10.1186/bcr3395 Sun, 2012, Double spiral microchannel for label-free tumor cell separation and enrichment, Lab Chip, 12, 3952, 10.1039/c2lc40679a Sun, 2013, Size-based hydrodynamic rare tumor cell separation in curved microfluidic channels, Biomicrofluidics, 7, 011802, 10.1063/1.4774311 Talasaz, 2009, Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device, Proc Natl Acad Sci U S A, 106, 3970, 10.1073/pnas.0813188106 Tan, 2010, Versatile label free biochip for the detection of circulating tumor cells from peripheral blood in cancer patients, Biosens Bioelectron, 26, 1701, 10.1016/j.bios.2010.07.054 Tan, 2009, Microdevice for the isolation and enumeration of cancer cells from blood, Biomed Microdevices, 11, 883, 10.1007/s10544-009-9305-9 Tewes, 2009, Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies, Breast Cancer Res Treat, 115, 581, 10.1007/s10549-008-0143-x Theodoropoulos, 2010, Circulating tumor cells with a putative stem cell phenotype in peripheral blood of patients with breast cancer, Cancer Lett, 288, 99, 10.1016/j.canlet.2009.06.027 Thiery, 2002, Epithelial–mesenchymal transitions in tumour progression, Nat Rev Cancer, 2, 442, 10.1038/nrc822 Tomlins, 2005, Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer, Science, 310, 644, 10.1126/science.1117679 Ushijima, 2009, Treatment for recurrent ovarian cancer—at first relapse, J Oncol, 2010 Vona, 2004, Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer, Hepatology, 39, 792, 10.1002/hep.20091 Vona, 2000, Isolation by size of epithelial tumor cells—a new method for the immunomorphological and molecular characterization of circulating tumor cells, Am J Pathol, 156, 57, 10.1016/S0002-9440(10)64706-2 Wang, 2000, Identification and characterization of circulating prostate carcinoma cells, Cancer, 88, 2787, 10.1002/1097-0142(20000615)88:12<2787::AID-CNCR18>3.0.CO;2-2 Wang, 2011, Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers, Angew Chem Int Ed, 50, 3084, 10.1002/anie.201005853 Wang, 2009, Three-dimensional nanostructured substrates toward efficient capture of circulating tumor cells, Angew Chem Int Ed Engl, 48, 8970, 10.1002/anie.200901668 Weitz, 1998, Dissemination of tumor cells in patients undergoing surgery for colorectal cancer, Clin Cancer Res, 4, 343 Wendel, 2012, Fluid biopsy for circulating tumor cell identification in patients with early-and late-stage non-small cell lung cancer: a glimpse into lung cancer biology, Phys Biol, 9, 016005, 10.1088/1478-3967/9/1/016005 Wulfing, 2006, HER2-positive circulating tumor cells indicate poor clinical outcome in stage I to III breast cancer patients, Clin Cancer Res, 12, 1715, 10.1158/1078-0432.CCR-05-2087 Xu, 2010, A cancer detection platform which measures telomerase activity from live circulating tumor cells captured on a microfilter, Cancer Res, 70, 6420, 10.1158/0008-5472.CAN-10-0686 Yang, 2009, Optimization of an enrichment process for circulating tumor cells from the blood of head and neck cancer patients through depletion of normal cells, Biotechnol Bioeng, 102, 521, 10.1002/bit.22066 Yu, 2013, Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition, Science, 339, 580, 10.1126/science.1228522 Yu, 2012, RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis, Nature, 487, 510, 10.1038/nature11217 Zhao, 2013, High-purity prostate circulating tumor cell isolation by a polymer nanofiber-embedded microchip for whole exome sequencing, Adv Mater, 25, 2897, 10.1002/adma.201205237 Zheng, 2007, Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells, J Chromatogr A, 1162, 154, 10.1016/j.chroma.2007.05.064 Zheng, 2011, 3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood, Biomed Microdevices, 13, 203, 10.1007/s10544-010-9485-3