Molecular analysis of circulating tumour cells—biology and biomarkers (original) (raw)
Schilsky, R. L. Personalized medicine in oncology: the future is now. Nat. Rev. Drug Discov.9, 363–366 (2010). ArticleCASPubMed Google Scholar
McDermott, U. & Settleman, J. Personalized cancer therapy with selective kinase inhibitors: an emerging paradigm in medical oncology. J. Clin. Oncol.27, 5650–5659 (2009). ArticleCASPubMed Google Scholar
Dancey, J. E., Bedard, P. L., Onetto, N. & Hudson, T. J. The genetic basis for cancer treatment decisions. Cell148, 409–420 (2012). ArticleCASPubMed Google Scholar
Dienstmann, R., Rodon, J. & Tabernero, J. Biomarker-driven patient selection for early clinical trials. Curr. Opin. Oncol.25, 305–312 (2013). ArticleCASPubMed Google Scholar
Shaw, A. T. et al. Crizotinib versus chemotherapy in advanced _ALK_-positive lung cancer. N. Engl. J. Med.368, 2385–2394 (2013). ArticleCASPubMed Google Scholar
Zhou, C. et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol.12, 735–742 (2011). ArticleCASPubMed Google Scholar
Mok, T. S. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med.361, 947–957 (2009). ArticleCASPubMed Google Scholar
Pao, W. et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med.2, e73 (2005). ArticleCASPubMedPubMed Central Google Scholar
Garraway, L. A. & Baselga, J. Whole-genome sequencing and cancer therapy: is too much ever enough? Cancer Discov.2, 766–768 (2012). ArticlePubMed Google Scholar
Gonzalez de Castro, D., Clarke, P. A., Al-Lazikani, B. & Workman, P. Personalized cancer medicine: molecular diagnostics, predictive biomarkers, and drug resistance. Clin. Pharmacol. Ther.93, 252–259 (2013). ArticleCASPubMedPubMed Central Google Scholar
Misale, S. et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature486, 532–536 (2012). ArticleCASPubMedPubMed Central Google Scholar
Wu, C. C., Maher, M. M. & Shepard, J. A. Complications of CT-guided percutaneous needle biopsy of the chest: prevention and management. AJR Am. J. Roentgenol.196, W678–W682 (2011). ArticlePubMed Google Scholar
Yachida, S. et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature467, 1114–1117 (2010). CASPubMedPubMed Central Google Scholar
Gerlinger, M. et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med.366, 883–892 (2012). ArticleCASPubMedPubMed Central Google Scholar
Greaves, M. F., Maia, A. T., Wiemels, J. L. & Ford, A. M. Leukemia in twins: lessons in natural history. Blood102, 2321–2333 (2003). ArticleCASPubMed Google Scholar
Bateman, C. M. et al. Acquisition of genome-wide copy number alterations in monozygotic twins with acute lymphoblastic leukemia. Blood115, 3553–3558 (2010). ArticleCASPubMed Google Scholar
Anderson, K. et al. Genetic variegation of clonal architecture and propagating cells in leukaemia. Nature469, 356–361 (2011). ArticleCASPubMed Google Scholar
Pantel, K. & Brakenhoff, R. H. Dissecting the metastatic cascade. Nat. Rev. Cancer4, 448–456 (2004). ArticleCASPubMed Google Scholar
Baccelli, I. et al. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat. Biotechnol.31, 539–544 (2013). ArticleCASPubMed Google Scholar
Yu, M., Stott, S., Toner, M., Maheswaran, S. & Haber, D. A. Circulating tumor cells: approaches to isolation and characterization. J. Cell Biol.192, 373–382 (2011). ArticleCASPubMedPubMed Central Google Scholar
Alix-Panabières, C. & Pantel, K. Circulating tumor cells: liquid biopsy of cancer. Clin. Chem.59, 110–118 (2013). ArticleCASPubMed Google Scholar
Hou, J. M. et al. Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer. J. Clin. Oncol.30, 525–532 (2012). ArticlePubMed Google Scholar
Krebs, M. G. et al. Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer. J. Clin. Oncol.29, 1556–1563 (2011). ArticlePubMed Google Scholar
de Bono, J. S. et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin. Cancer Res.14, 6302–6309 (2008). ArticleCASPubMed Google Scholar
Cohen, S. J. 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.26, 3213–3221 (2008). ArticlePubMed Google Scholar
Cristofanilli, M. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N. Engl. J. Med.351, 781–791 (2004). ArticleCASPubMed Google Scholar
Khan, M. S. et al. Circulating tumor cells as prognostic markers in neuroendocrine tumors. J. Clin. Oncol.31, 365–372 (2013). ArticleCASPubMed Google Scholar
Khoja, L. et al. Biomarker utility of circulating tumor cells in metastatic cutaneous melanoma. J. Invest. Dermatol.133, 1582–1590 (2013). ArticleCASPubMed Google Scholar
Hiraiwa, K. et al. Clinical significance of circulating tumor cells in blood from patients with gastrointestinal cancers. Ann. Surg. Oncol.15, 3092–3100 (2008). ArticlePubMed Google Scholar
Devriese, L. A., Voest, E. E., Beijnen, J. H. & Schellens, J. H. Circulating tumor cells as pharmacodynamic biomarker in early clinical oncological trials. Cancer Treat. Rev.37, 579–589 (2011). ArticleCASPubMed Google Scholar
Pailler, E. et al. Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer. J. Clin. Oncol.31, 2273–2281 (2013). ArticlePubMed Google Scholar
Pestrin, M. et al. Correlation of HER2 status between primary tumors and corresponding circulating tumor cells in advanced breast cancer patients. Breast Cancer Res. Treat.118, 523–530 (2009). ArticleCASPubMed Google Scholar
Attard, G. et al. Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res.69, 2912–2918 (2009). ArticleCASPubMed Google Scholar
Schneck, H. et al. Analysing the mutational status of PIK3CA in circulating tumor cells from metastatic breast cancer patients. Mol. Oncol.7, 976–986 (2013). ArticleCASPubMedPubMed Central Google Scholar
Zhang, L. et al. The identification and characterization of breast cancer CTCs competent for brain metastasis. Sci. Transl. Med.5, 180ra148 (2013). ArticleCAS Google Scholar
Tang, F. et al. mRNA-Seq whole-transcriptome analysis of a single cell. Nat. Methods6, 377–382 (2009). ArticleCASPubMed Google Scholar
Ramsköld, D. et al. Full-length mRNA-Seq from single-cell levels of RNA and individual circulating tumor cells. Nat. Biotechnol.30, 777–782 (2012). ArticleCASPubMedPubMed Central Google Scholar
Thiery, J. P. Epithelial–mesenchymal transitions in tumour progression. Nat. Rev. Cancer2, 442–454 (2002). ArticleCASPubMed Google Scholar
Thiery, J. P. & Lim, C. T. Tumor dissemination: an EMT affair. Cancer Cell23, 272–273 (2013). ArticleCASPubMed Google Scholar
Tsuji, T., Ibaragi, S. & Hu, G. F. Epithelial–mesenchymal transition and cell cooperativity in metastasis. Cancer Res.69, 7135–7139 (2009). ArticleCASPubMedPubMed Central Google Scholar
Tsuji, T. et al. Epithelial–mesenchymal transition induced by growth suppressor p12CDK2–AP1 promotes tumor cell local invasion but suppresses distant colony growth. Cancer Res.68, 10377–10386 (2008). ArticleCASPubMedPubMed Central Google Scholar
Calbo, J. et al. A functional role for tumor cell heterogeneity in a mouse model of small cell lung cancer. Cancer Cell19, 244–256 (2011). ArticleCASPubMed Google Scholar
Duda, D. G. et al. Malignant cells facilitate lung metastasis by bringing their own soil. Proc. Natl Acad. Sci. USA107, 21677–21682 (2010). ArticlePubMedPubMed Central Google Scholar
Friedl, P. et al. Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro. Cancer Res.55, 4557–4560 (1995). CASPubMed Google Scholar
Bednarz-Knoll, N., Alix-Panabières, C. & Pantel, K. Clinical relevance and biology of circulating tumor cells. Breast Cancer Res.13, 228 (2011). ArticlePubMedPubMed Central Google Scholar
Vona, G. et al. Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulating tumor cells. Am. J. Pathol.156, 57–63 (2000). ArticleCASPubMedPubMed Central Google Scholar
Müller, V. et al. Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity. Clin. Cancer Res.11, 3678–3685 (2005). ArticlePubMed Google Scholar
Gascoyne, P. R., Noshari, J., Anderson, T. J. & Becker, F. F. Isolation of rare cells from cell mixtures by dielectrophoresis. Electrophoresis30, 1388–1398 (2009). ArticleCASPubMedPubMed Central Google Scholar
Moon, H. S. et al. Continuous separation of breast cancer cells from blood samples using multi-orifice flow fractionation (MOFF) and dielectrophoresis (DEP). Lab Chip11, 1118–1125 (2011). ArticleCASPubMed Google Scholar
Allard, W. J. et al. 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 (2004). ArticlePubMed Google Scholar
Riethdorf, S. et al. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: a validation study of the CellSearch system. Clin. Cancer Res.13, 920–928 (2007). ArticleCASPubMed Google Scholar
Talasaz, A. H. et al. Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc. Natl Acad. Sci. USA106, 3970–3975 (2009). ArticlePubMedPubMed Central Google Scholar
Saucedo-Zeni, N. et al. 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, 1241–1250 (2012). PubMedPubMed Central Google Scholar
Nagrath, S. et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature450, 1235–1239 (2007). ArticleCASPubMedPubMed Central Google Scholar
Stott, S. L. et al. Isolation of circulating tumor cells using a microvortex-generating herringbone-chip. Proc. Natl Acad. Sci. USA107, 18392–18397 (2010). ArticlePubMedPubMed Central Google Scholar
Ozkumur, E. et al. Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells. Sci. Transl. Med.5, 179ra147 (2013). ArticleCAS Google Scholar
Saliba, A. E. et al. Microfluidic sorting and multimodal typing of cancer cells in self-assembled magnetic arrays. Proc. Natl Acad. Sci. USA107, 14524–14529 (2010). ArticlePubMedPubMed Central Google Scholar
Zieglschmid, V. et al. Combination of immunomagnetic enrichment with multiplex RT-PCR analysis for the detection of disseminated tumor cells. Anticancer Res.25, 1803–1810 (2005). CASPubMed Google Scholar
Harb, W. et al. Mutational analysis of circulating tumor cells using a novel microfluidic collection device and qPCR assay. Transl. Oncol.6, 528–538 (2013). ArticlePubMedPubMed Central Google Scholar
Vona, G. et al. Impact of cytomorphological detection of circulating tumor cells in patients with liver cancer. Hepatology39, 792–797 (2004). ArticlePubMed Google Scholar
Alix-Panabieres, C. EPISPOT assay: detection of viable DTCs/CTCs in solid tumor patients. Recent Results Cancer Res.195, 69–76 (2012). ArticlePubMed Google Scholar
Lu, J. et al. Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients. Int. J. Cancer126, 669–683 (2010). ArticleCASPubMedPubMed Central Google Scholar
López-Riquelme, N. et al. Imaging cytometry for counting circulating tumor cells: comparative analysis of the CellSearch vs Image Stream systems. APMIShttp://dx.doi.org/10.1111/apm.12061.
Marrinucci, D. et al. Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers. Phys. Biol.9, 016003 (2012). ArticlePubMedPubMed Central Google Scholar
Kraan, J. et al. External quality assurance of circulating tumor cell enumeration using the CellSearch® system: a feasibility study. Cytometry B Clin. Cytom.80, 112–118 (2011). ArticlePubMed Google Scholar
Parkinson, D. R. et al. Considerations in the development of circulating tumor cell technology for clinical use. J. Transl. Med.10, 138 (2012). ArticlePubMedPubMed Central Google Scholar
Stathopoulou, A. 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.9, 5145–5151 (2003). CASPubMed Google Scholar
Xenidis, N. et al. Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer. J. Clin. Oncol.27, 2177–2184 (2009). ArticleCASPubMed Google Scholar
Iinuma, H. et al. 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, 1547–1555 (2011). ArticlePubMed Google Scholar
Chimonidou, M., Kallergi, G., Georgoulias, V., Welch, D. R. & Lianidou, E. S. Breast cancer metastasis suppressor-1 promoter methylation provides prognostic information in primary breast tumors. Mol. Cancer Res.11, 1248–1257 (2013). ArticleCASPubMed Google Scholar
Chen, C. L. et al. Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer. Prostate73, 813–826 (2013). ArticleCASPubMed Google Scholar
Fabbri, F. et al. Detection and recovery of circulating colon cancer cells using a dielectrophoresis-based device: KRAS mutation status in pure CTCs. Cancer Lett.335, 225–231 (2013). ArticleCASPubMed Google Scholar
Peeters, D. J. et al. Semiautomated isolation and molecular characterisation of single or highly purified tumour cells from CellSearch enriched blood samples using dielectrophoretic cell sorting. Br. J. Cancer108, 1358–1367 (2013). ArticleCASPubMedPubMed Central Google Scholar
Punnoose, E. A. et al. Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin. Cancer Res.18, 2391–2401 (2012). ArticleCASPubMed Google Scholar
Gasch, C. 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.59, 252–260 (2013). ArticleCASPubMed Google Scholar
Voet, T. et al. Single-cell paired-end genome sequencing reveals structural variation per cell cycle. Nucleic Acids Res.41, 6119–6138 (2013). ArticleCASPubMedPubMed Central Google Scholar
Dean, F. B. et al. Comprehensive human genome amplification using multiple displacement amplification. Proc. Natl Acad. Sci. USA99, 5261–5266 (2002). ArticleCASPubMedPubMed Central Google Scholar
De Roock, W. et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol.11, 753–762 (2010). ArticleCASPubMed Google Scholar
Klein, C. A. et al. Combined transcriptome and genome analysis of single micrometastatic cells. Nat. Biotechnol.20, 387–392 (2002). ArticleCASPubMed Google Scholar
Ulmer, A. et al. Immunomagnetic enrichment, genomic characterization, and prognostic impact of circulating melanoma cells. Clin. Cancer Res.10, 531–537 (2004). ArticleCASPubMed Google Scholar
Heitzer, E. et al. Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res.73, 2965–2975 (2013). ArticleCASPubMed Google Scholar
Powell, A. A. et al. Single cell profiling of circulating tumor cells: transcriptional heterogeneity and diversity from breast cancer cell lines. PLoS ONE7, e33788 (2012). ArticleCASPubMedPubMed Central Google Scholar
Cann, G. M. et al. mRNA-Seq of single prostate cancer circulating tumor cells reveals recapitulation of gene expression and pathways found in prostate cancer. PLoS ONE7, e49144 (2012). ArticleCASPubMedPubMed Central Google Scholar
Asare, A. L. et al. Differential gene expression profiles are dependent upon method of peripheral blood collection and RNA isolation. BMC Genomics9, 474 (2008). ArticleCASPubMedPubMed Central Google Scholar
Fidler, I. J. The relationship of embolic homogeneity, number, size and viability to the incidence of experimental metastasis. Eur. J. Cancer9, 223–227 (1973). ArticleCASPubMed Google Scholar
Liotta, L. A., Kleinerman, J. & Saidel, G. M. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res.34, 997–1004 (1974). CASPubMed Google Scholar
Liotta, L. A., Saidel, M. G. & Kleinerman, J. The significance of hematogenous tumor cell clumps in the metastatic process. Cancer Res.36, 889–894 (1976). CASPubMed Google Scholar
Garvie, W. H. & Matheson, A. B. The effect of intravenous fluids on the development on experimental tumour metastases: their effect on tumour cell aggregation. Br. J. Cancer20, 838–846 (1966). ArticleCASPubMedPubMed Central Google Scholar
Lione, A. & Bosmann, H. B. Quantitative relationship between volume of tumour cell units and their intravascular survival. Br. J. Cancer37, 248–253 (1978). ArticleCASPubMedPubMed Central Google Scholar
Topal, B., Roskams, T., Fevery, J. & Penninckx, F. Aggregated colon cancer cells have a higher metastatic efficiency in the liver compared with nonaggregated cells: an experimental study. J. Surg. Res.112, 31–37 (2003). ArticleCASPubMed Google Scholar
Knisely, W. H. & Mahaley, M. S. Jr. Relationship between size and distribution of spontaneous metastases and three sizes of intravenously injected particles of VX2 carcinoma. Cancer Res.18, 900–905 (1958). CASPubMed Google Scholar
Thompson, S. C. The colony forming efficiency of single cells and cell aggregates from a spontaneous mouse mammary tumour using the lung colony assay. Br. J. Cancer30, 332–336 (1974). ArticleCASPubMedPubMed Central Google Scholar
Edelman, G. M., Gallin, W. J., Delouvée, A., Cunningham, B. A. & Thiery, J. P. Early epochal maps of two different cell adhesion molecules. Proc. Natl Acad. Sci. USA80, 4384–4388 (1983). ArticleCASPubMedPubMed Central Google Scholar
Kim, K. K. et al. Alveolar epithelial cell mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc. Natl Acad. Sci. USA103, 13180–13185 (2006). ArticleCASPubMedPubMed Central Google Scholar
Soltermann, A. et al. Prognostic significance of epithelial–mesenchymal and mesenchymal–epithelial transition protein expression in non-small cell lung cancer. Clin. Cancer Res.14, 7430–7437 (2008). ArticleCASPubMed Google Scholar
Bellovin, D. I. et al. Reciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma. Oncogene25, 6959–6967 (2006). ArticleCASPubMed Google Scholar
Gjerdrum, C. et al. Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival. Proc. Natl Acad. Sci. USA107, 1124–1129 (2010). ArticlePubMed Google Scholar
Otsuki, S. et al. Vimentin expression is associated with decreased survival in gastric cancer. Oncol. Rep.25, 1235–1242 (2011). PubMed Google Scholar
Lee, K. W. et al. Twist1 is an independent prognostic factor of esophageal squamous cell carcinoma and associated with its epithelial-mesenchymal transition. Ann. Surg. Oncol.19, 326–335 (2012). ArticlePubMed Google Scholar
Byers, L. A. et al. An epithelial–mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance. Clin. Cancer Res.19, 279–290 (2013). ArticleCASPubMed Google Scholar
Kurokawa, M., Ise, N., Omi, K., Goishi, K. & Higashiyama, S. Cisplatin influences acquisition of resistance to molecular-targeted agents through epithelial-mesenchymal transition-like changes. Cancer Sci.104, 904–911 (2013). ArticleCASPubMedPubMed Central Google Scholar
Yauch, R. L. et al. Epithelial versus mesenchymal phenotype determines in vitro sensitivity and predicts clinical activity of erlotinib in lung cancer patients. Clin. Cancer Res.11, 8686–8698 (2005). ArticleCASPubMed Google Scholar
Lim, S. et al. SNAI1-mediated epithelial-mesenchymal transition confers chemoresistance and cellular plasticity by regulating genes involved in cell death and stem cell maintenance. PLoS ONE8, e66558 (2013). ArticleCASPubMedPubMed Central Google Scholar
Brabletz, T. et al. Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc. Natl Acad. Sci. USA98, 10356–10361 (2001). ArticleCASPubMedPubMed Central Google Scholar
Stark, K., Vainio, S., Vassileva, G. & McMahon, A. P. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature372, 679–683 (1994). ArticleCASPubMed Google Scholar
Hou, J. M. et al. Circulating tumor cells as a window on metastasis biology in lung cancer. Am. J. Pathol.178, 989–996 (2011). ArticlePubMedPubMed Central Google Scholar
Lecharpentier, A. et al. Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer. Br. J. Cancer105, 1338–1341 (2011). ArticleCASPubMedPubMed Central Google Scholar
Kallergi, G. et al. Epithelial to mesenchymal transition markers expressed in circulating tumour cells of early and metastatic breast cancer patients. Breast Cancer Res.13, R59 (2011). ArticlePubMedPubMed Central Google Scholar
Armstrong, A. J. et al. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol. Cancer Res.9, 997–1007 (2011). ArticleCASPubMedPubMed Central Google Scholar
Balasubramanian, P. et al. Multiparameter analysis, including EMT markers, on negatively enriched blood samples from patients with squamous cell carcinoma of the head and neck. PLoS ONE7, e42048 (2012). ArticleCASPubMedPubMed Central Google Scholar
Yu, M. et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science339, 580–584 (2013). ArticleCASPubMedPubMed Central Google Scholar
Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J. & Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl Acad. Sci. USA100, 3983–3988 (2003). ArticleCASPubMedPubMed Central Google Scholar
Singh, S. K. et al. Identification of a cancer stem cell in human brain tumors. Cancer Res.63, 5821–5828 (2003). CASPubMed Google Scholar
Ricci-Vitiani, L. et al. Identification and expansion of human colon-cancer-initiating cells. Nature445, 111–115 (2007). ArticleCASPubMed Google Scholar
Chan, K. S. et al. Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Proc. Natl Acad. Sci. USA106, 14016–14021 (2009). ArticlePubMedPubMed Central Google Scholar
Stewart, J. M. et al. Phenotypic heterogeneity and instability of human ovarian tumor-initiating cells. Proc. Natl Acad. Sci. USA108, 6468–6473 (2011). ArticlePubMedPubMed Central Google Scholar
Reya, T., Morrison, S. J., Clarke, M. F. & Weissman, I. L. Stem cells, cancer, and cancer stem cells. Nature414, 105–111 (2001). ArticleCASPubMed Google Scholar
Grimshaw, M. J. et al. Mammosphere culture of metastatic breast cancer cells enriches for tumorigenic breast cancer cells. Breast Cancer Res.10, R52 (2008). ArticleCASPubMedPubMed Central Google Scholar
Fidler, I. J. Metastasis: quantitative analysis of distribution and fate of tumor embolilabeled with 125 I-5-iodo-2′-deoxyuridine. J. Natl Cancer Inst.45, 773–782 (1970). CASPubMed Google Scholar
Luzzi, K. J. et al. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am. J. Pathol.153, 865–873 (1998). ArticleCASPubMedPubMed Central Google Scholar
Chambers, A. F., Groom, A. C. & MacDonald, I. C. Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer2, 563–572 (2002). ArticleCASPubMed Google Scholar
Fidler, I. J. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat. Rev. Cancer3, 453–458 (2003). ArticleCASPubMed Google Scholar
Chaffer, C. L. & Weinberg, R. A. A perspective on cancer cell metastasis. Science331, 1559–1564 (2011). ArticleCASPubMed Google Scholar
Zhao, Q. et al. Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis. Mol. Cancer9, 154 (2010). ArticleCASPubMedPubMed Central Google Scholar
Fidler, I. J. Immune stimulation-inhibition of experimental cancer metastasis. Cancer Res.34, 491–498 (1974). CASPubMed Google Scholar
Ludatscher, R. M., Luse, S. A. & Suntzeff, V. An electron microscopic study of pulmonary tumor emboli from transplantable Morris hepatoma 5123. Cancer Res.27, 1939–1952 (1967). CASPubMed Google Scholar
Sugino, T. et al. An invasion-independent pathway of blood-borne metastasis: a new murine mammary tumor model. Am. J. Pathol.160, 1973–1980 (2002). ArticleCASPubMedPubMed Central Google Scholar
Küsters, B. et al. Micronodular transformation as a novel mechanism of VEGF-A-induced metastasis. Oncogene26, 5808–5815 (2007). ArticleCASPubMed Google Scholar
Laübli, H., Stevenson, J. L., Varki, A., Varki, N. M. & Borsig, L. L-Selectin facilitation of metastasis involves temporal induction of Fut7-dependent ligands at sites of tumor cell arrest. Cancer Res.66, 1536–1542 (2006). ArticleCASPubMed Google Scholar
Gasic, G. J., Gasic, T. B., Galanti, N., Johnson, T. & Murphy, S. Platelet-tumor-cell interactions in mice. The role of platelets in the spread of malignant disease. Int. J. Cancer11, 704–718 (1973). ArticleCASPubMed Google Scholar
Borsig, L., Wong, R., Hynes, R. O., Varki, N. M. & Varki, A. Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc. Natl Acad. Sci. USA99, 2193–2198 (2002). ArticleCASPubMedPubMed Central Google Scholar
Upreti, M. et al. Tumor-endothelial cell three-dimensional spheroids: new aspects to enhance radiation and drug therapeutics. Transl. Oncol.4, 365–376 (2011). ArticlePubMedPubMed Central Google Scholar
Fidler, I. J. & Talmadge, J. E. Evidence that intravenously derived murine pulmonary melanoma metastases can originate from the expansion of a single tumor cell. Cancer Res.46, 5167–5171 (1986). CASPubMed Google Scholar
Talmadge, J. E., Wolman, S. R. & Fidler, I. J. Evidence for the clonal origin of spontaneous metastases. Science217, 361–363 (1982). ArticleCASPubMed Google Scholar
Krebs, M. G. et al. Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. J. Thorac. Oncol.7, 306–315 (2012). ArticlePubMed Google Scholar
Tomlinson, J. S., Alpaugh, M. L. & Barsky, S. H. An intact overexpressed E-cadherin/α, β-catenin axis characterizes the lymphovascular emboli of inflammatory breast carcinoma. Cancer Res.61, 5231–5241 (2001). CASPubMed Google Scholar
Kleer, C. G., van Golen, K. L., Braun, T. & Merajver, S. D. Persistent E-cadherin expression in inflammatory breast cancer. Mod. Pathol.14, 458–464 (2001). ArticleCASPubMed Google Scholar
Sugino, T. et al. Morphological evidence for an invasion-independent metastasis pathway exists in multiple human cancers. BMC Med.2, 9 (2004). ArticlePubMedPubMed Central Google Scholar
De Giorgi, U. et al. Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer. Ann. Oncol.21, 33–39 (2010). ArticleCASPubMed Google Scholar
Cho, E. H. et al. Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors. Phys. Biol.9, 016001 (2012). ArticlePubMedPubMed Central Google Scholar
Griffiths, J. D., McKinna, J. A., Rowbotham, H. D., Tsolakidis, P. & Salsbury, A. J. Carcinoma of the colon and rectum: circulating malignant cells and five-year survival. Cancer31, 226–236 (1973). ArticleCASPubMed Google Scholar
Hofman, V. et al. 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, 827–835 (2011). ArticleCASPubMed Google Scholar
Kats-Ugurlu, G. et al. Circulating tumour tissue fragments in patients with pulmonary metastasis of clear cell renal cell carcinoma. J. Pathol.219, 287–293 (2009). ArticleCASPubMed Google Scholar
Glaves, D., Huben, R. P. & Weiss, L. Haematogenous dissemination of cells from human renal adenocarcinomas. Br. J. Cancer57, 32–35 (1988). ArticleCASPubMedPubMed Central Google Scholar
Brandt, B. et al. Isolation of prostate-derived single cells and cell clusters from human peripheral blood. Cancer Res.56, 4556–4561 (1996). CASPubMed Google Scholar
Molnar, B., Ladanyi, A., Tanko, L., Sréter, L. & Tulassay, Z. Circulating tumor cell clusters in the peripheral blood of colorectal cancer patients. Clin. Cancer Res.7, 4080–4085 (2001). CASPubMed Google Scholar
Wang, Z. P. et al. Identification and characterization of circulating prostate carcinoma cells. Cancer88, 2787–2795 (2000). ArticleCASPubMed Google Scholar
Krebs, M. G., Hou, J.-M., Ward, T. H., Blackhall, F. H. & Dive, C. Circulating tumour cells: their utility in cancer management and predicting outcomes. Ther. Adv. Med. Oncol.2, 351–365 (2010). ArticlePubMedPubMed Central Google Scholar
Gorges, T. M. & Pantel, K. Circulating tumor cells as therapy-related biomarkers in cancer patients. Cancer Immunol. Immunother.62, 931–939 (2013). ArticleCASPubMed Google Scholar
Stott, S. L. et al. Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. Sci. Transl. Med.2, 25ra23 (2010). ArticleCASPubMedPubMed Central Google Scholar
Hiltermann, T. J. et al. Circulating tumor cells in small-cell lung cancer: a predictive and prognostic factor. Ann. Oncol.23, 2937–2942 (2012). ArticleCASPubMed Google Scholar
Naito, T. et al. Prognostic impact of circulating tumor cells in patients with small cell lung cancer. J. Thorac. Oncol.7, 512–519 (2012). ArticlePubMed Google Scholar
Hayes, D. F. et al. 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, 4218–4224 (2006). ArticleCASPubMed Google Scholar
Riethdorf, S. et al. 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 (2010). ArticleCASPubMed Google Scholar
de Bono, J. S. et al. Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor. Clin. Cancer Res.13, 3611–3616 (2007). ArticleCASPubMed Google Scholar
Liu, Z. et al. Eradication of EGFR-positive circulating tumor cells and objective tumor response with lapatinib and capecitabine. Cancer Biol. Ther.10, 860–864 (2010). ArticleCASPubMed Google Scholar
Evans, W. K. et al. Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer. J. Clin. Oncol.3, 65–71 (1985). ArticleCASPubMed Google Scholar
Bidard, F. C. et al. Clinical application of circulating tumor cells in breast cancer: overview of the current interventional trials. Cancer Metastasis Rev.32, 179–188 (2013). ArticlePubMed Google Scholar
Swennenhuis, J. F., Tibbe, A. G., Levink, R., Sipkema, R. C. & Terstappen, L. W. Characterization of circulating tumor cells by fluorescence in situ hybridization. Cytometry A75, 520–527 (2009). ArticleCASPubMed Google Scholar
Rossi, E. et al. M30 neoepitope expression in epithelial cancer: quantification of apoptosis in circulating tumor cells by CellSearch analysis. Clin. Cancer Res.16, 5233–5243 (2010). ArticleCASPubMed Google Scholar
Ang, J. E., Kaye, S. & Banerji, U. Tissue-based approaches to study pharmacodynamic endpoints in early phase oncology clinical trials. Curr. Drug Targets13, 1525–1534 (2012). ArticleCASPubMedPubMed Central Google Scholar
Wang, L. H. et al. Monitoring drug-induced gammaH2AX as a pharmacodynamic biomarker in individual circulating tumor cells. Clin. Cancer Res.16, 1073–1084 (2010). ArticleCASPubMedPubMed Central Google Scholar
Kallergi, G. et al. Phosphorylated EGFR and PI3K/Akt signaling kinases are expressed in circulating tumor cells of breast cancer patients. Breast Cancer Res.10, R80 (2008). ArticleCASPubMedPubMed Central Google Scholar
Flores, L. M. et al. Improving the yield of circulating tumour cells facilitates molecular characterisation and recognition of discordant HER2 amplification in breast cancer. Br. J. Cancer102, 1495–1502 (2010). ArticleCASPubMedPubMed Central Google Scholar
Kallergi, G. et al. Hypoxia-inducible factor-1α and vascular endothelial growth factor expression in circulating tumor cells of breast cancer patients. Breast Cancer Res.11, R84 (2009). ArticleCASPubMedPubMed Central Google Scholar
Camidge, D. R. et al. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol.13, 1011–1019 (2012). ArticleCASPubMedPubMed Central Google Scholar
Ilie, M. et al. ALK-gene rearrangement: a comparative analysis on circulating tumour cells and tumour tissue from patients with lung adenocarcinoma. Ann. Oncol.23, 2907–2913 (2012). ArticleCASPubMed Google Scholar
Hayes, D. F. et al. Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer. Int. J. Oncol.21, 1111–1117 (2002). CASPubMed Google Scholar
Jiang, Y., Palma, J. F., Agus, D. B., Wang, Y. & Gross, M. E. Detection of androgen receptor mutations in circulating tumor cells in castration-resistant prostate cancer. Clin. Chem.56, 1492–1495 (2010). ArticlePubMed Google Scholar
Leversha, M. A. et al. Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer. Clin. Cancer Res.15, 2091–2097 (2009). ArticleCASPubMedPubMed Central Google Scholar
Liu, Y. et al. Circulating tumor cells in HER2-positive metastatic breast cancer patients: a valuable prognostic and predictive biomarker. BMC Cancer13, 202 (2013). ArticleCASPubMedPubMed Central Google Scholar
Crowley, E., Di Nicolantonio, F., Loupakis, F. & Bardelli, A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat. Rev. Clin. Oncol.10, 472–484 (2013). ArticleCASPubMed Google Scholar
De Mattos-Arruda, L. et al. Circulating tumour cells and cell-free DNA as tools for managing breast cancer. Nat. Rev. Clin. Oncol.10, 377–389 (2013). ArticleCASPubMed Google Scholar
Dawson, S. J. et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N. Engl. J. Med.368, 1199–1209 (2013). ArticleCASPubMed Google Scholar
Cristofanilli, M. & Fortina, P. Circulating tumor DNA to monitor metastatic breast cancer. N. Engl. J. Med.369, 93–94 (2013). ArticlePubMed Google Scholar
Taniguchi, K. et al. Quantitative detection of EGFR mutations in circulating tumor DNA derived from lung adenocarcinomas. Clin. Cancer Res.17, 7808–7815 (2011). ArticleCASPubMed Google Scholar
Murtaza, M. et al. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature497, 108–112 (2013). ArticleCASPubMed Google Scholar
Hofman, P. et al. Immunohistochemistry to identify EGFR mutations or ALK rearrangements in patients with lung adenocarcinoma. Ann. Oncol.23, 1738–1743 (2012). ArticleCASPubMed Google Scholar
Ni, X. et al. Reproducible copy number variation patterns among single circulating tumor cells of lung cancer patients. Proc. Natl Acad. Sci. USA110, 21083–21088 (2013). ArticleCASPubMedPubMed Central Google Scholar