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Circulating tumor cell information


An illustration depicting primary tumor (in the form of tumor microenvironment) and the circulating tumor cells.

A circulating tumor cell (CTC) is a cell that has shed into the vasculature or lymphatics[1] from a primary tumor and is carried around the body in the blood circulation. CTCs can extravasate and become seeds for the subsequent growth of additional tumors (metastases) in distant organs, a mechanism that is responsible for the vast majority of cancer-related deaths.[2] The detection and analysis of CTCs can assist early patient prognoses and determine appropriate tailored treatments.[3] Currently, there is one FDA-approved method for CTC detection, CellSearch, which is used to diagnose breast, colorectal and prostate cancer.[4]

The detection of CTCs, or liquid biopsy, presents several advantages over traditional tissue biopsies. They are non-invasive, can be used repeatedly, and provide more useful information on metastatic risk, disease progression, and treatment effectiveness.[5][6] For example, analysis of blood samples from cancer patients has found a propensity for increased CTC detection as the disease progresses.[7] Blood tests are easy and safe to perform and multiple samples can be taken over time. By contrast, analysis of solid tumors necessitates invasive procedures that might limit patient compliance. The ability to monitor the disease progression over time could facilitate appropriate modification to a patient's therapy, potentially improving their prognosis and quality of life. The important aspect of the ability to prognose the future progression of the disease is elimination (at least temporarily) of the need for a surgery when the repeated CTC counts are low and not increasing; the obvious benefits of avoiding the surgery include avoiding the risk related to the innate tumor-genicity of cancer surgeries. To this end, technologies with the requisite sensitivity and reproducibility to detect CTCs in patients with metastatic disease have recently been developed.[8][9][10][11][12][13][14][15] On the other hand, CTCs are very rare, often present as only a few cells per milliliter of blood, which makes their detection challenging. In addition, they often express a variety of markers which vary from patient to patient, which makes it difficult to develop techniques with high sensitivity and specificity.

  1. ^ Riquet, M; Rivera, C; Gibault, L; Pricopi, C; Mordant, P; Badia, A; Arame, A; Le Pimpec Barthes, F (2014). "[Lymphatic spread of lung cancer: anatomical lymph node chains unchained in zones]". Revue de Pneumologie Clinique. 70 (1–2): 16–25. doi:10.1016/j.pneumo.2013.07.001. PMID 24566031.
  2. ^ Gupta, GP; Massagué, J (Nov 17, 2006). "Cancer metastasis: building a framework". Cell. 127 (4): 679–95. doi:10.1016/j.cell.2006.11.001. PMID 17110329. S2CID 7362869.
  3. ^ Rack B, Schindlbeck C, Jückstock J, Andergassen U, Hepp P, Zwingers T, Friedl T, Lorenz R, Tesch H, Fasching P, Fehm T, Schneeweiss A, Lichtenegger W, Beckmann M, Friese K, Pantel K, Janni W (2014). "Circulating Tumor Cells Predict Survival in Early Average-to-High Risk Breast Cancer Patients". Journal of the National Cancer Institute. 106 (5). doi:10.1093/jnci/dju066. PMC 4112925. PMID 24832787.
  4. ^ Millner, LM; Linder, MW; Valdes R, Jr (Summer 2013). "Circulating tumor cells: a review of present methods and the need to identify heterogeneous phenotypes". Annals of Clinical and Laboratory Science. 43 (3): 295–304. PMC 5060940. PMID 23884225.
  5. ^ Marrinucci, D; Bethel, K; Luttgen, M; Nieva, J; Kuhn, P; Kuhn, P (Sep 2009). "Circulating tumor cells from well-differentiated lung adenocarcinoma retain cytomorphologic features of primary tumor type". Archives of Pathology & Laboratory Medicine. 133 (9): 1468–71. doi:10.5858/133.9.1468. PMC 4422331. PMID 19722757.
  6. ^ Attard G, Swennenhuis JF, Olmos D, Reid AH, Vickers E, A'Hern R, Levink R, Coumans F, Moreira J, Riisnaes R, Oommen NB, Hawche G, Jameson C, Thompson E, Sipkema R, Carden CP, Parker C, Dearnaley D, Kaye SB, Cooper CS, Molina A, Cox ME, Terstappen LW, de Bono JS (2009). "Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer". Cancer Res. 69 (7): 2912–8. doi:10.1158/0008-5472.CAN-08-3667. PMID 19339269.
  7. ^ 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 (19): 3213–21. doi:10.1200/JCO.2007.15.8923. PMID 18591556.
  8. ^ Yu M, Ting DT, Stott SL, Wittner BS, Ozsolak F, Paul S, Ciciliano JC, Smas ME, Winokur D, Gilman AJ, Ulman MJ, Xega K, Contino G, Alagesan B, Brannigan BW, Milos PM, Ryan DP, Sequist LV, Bardeesy N, Ramaswamy S, Toner M, Maheswaran S, Haber DA (2012). "RNA sequencing of pancreatic circulating tumour cells implicates WNT signalling in metastasis". Nature. 487 (7408): 510–3. Bibcode:2012Natur.487..510Y. doi:10.1038/nature11217. PMC 3408856. PMID 22763454.
  9. ^ Sleijfer S, Gratama JW, Sieuwerts AM, et al. (2007). "Circulating tumour cell detection on its way to routine diagnostic implementation?". Eur J Cancer. 43 (18): 2645–50. doi:10.1016/j.ejca.2007.09.016. PMID 17977713.
  10. ^ Hayes DF, Smerage J.; Smerage (2008). "Is There a Role for Circulating Tumor Cells in the Management of Breast Cancer?". Clin Cancer Res. 14 (12): 3646–50. doi:10.1158/1078-0432.CCR-07-4481. PMID 18559576.
  11. ^ Pantel K, Alix-Panabières C, Riethdorf S (2009). "Cancer micrometastases". Nat Rev Clin Oncol. 6 (6): 339–51. doi:10.1038/nrclinonc.2009.44. PMID 19399023. S2CID 890927.
  12. ^ Pantel K, Riethdorf S.; Riethdorf (2009). "Pathology: are circulating tumor cells predictive of overall survival?". Nature Reviews Clinical Oncology. 6 (4): 190–1. doi:10.1038/nrclinonc.2009.23. PMID 19333222. S2CID 8904131.
  13. ^ Panteleakou Z, Lembessis P, Sourla A, et al. (2009). "Detection of circulating tumor cells in prostate cancer patients: methodological pitfalls and clinical relevance". Mol Med. 15 (3–4): 101–14. doi:10.2119/molmed.2008.00116. PMC 2600498. PMID 19081770.
  14. ^ Esmaeilsabzali H, Beischlag TV, Cox ME, Parameswaran AM, Park EJ (2013). "Detection and isolation of circulating tumor cells: principles and methods". Biotechnol. Adv. 31 (7): 1063–84. doi:10.1016/j.biotechadv.2013.08.016. PMID 23999357.
  15. ^ Nieva, J; Wendel, M; Luttgen, MS; Marrinucci, D; Bazhenova, L; Kolatkar, A; Santala, R; Whittenberger, B; Burke, J; Torrey, M; Bethel, K; Kuhn, P (Feb 2012). "High-definition imaging of circulating tumor cells and associated cellular events in non-small cell lung cancer patients: a longitudinal analysis". Physical Biology. 9 (1): 016004. Bibcode:2012PhBio...9a6004N. doi:10.1088/1478-3975/9/1/016004. PMC 3388002. PMID 22306961.

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Circulating tumor cell

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A circulating tumor cell (CTC) is a cell that has shed into the vasculature or lymphatics from a primary tumor and is carried around the body in the blood...

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Circulating tumor DNA

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Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the bloodstream that is not associated with cells. ctDNA should not be confused with cell-free...

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Biopsy

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of cell-free circulating tumor DNA (cfDNA) has an advantage over circulating tumor cells assays in that there is approximately 100 times more cell-free...

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Metastasis

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invasion to a second site for tumorigenesis. Some cancer cells known as circulating tumor cells acquire the ability to penetrate the walls of lymphatic...

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Cell isolation

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Methods for Circulating Tumor Cell Isolation and Molecular Analysis". Isolation and Molecular Characterization of Circulating Tumor Cells. Advances in...

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Circulating free DNA

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forms of DNA freely circulating in body fluids, including circulating tumor DNA (ctDNA), cell-free mitochondrial DNA (ccf mtDNA), cell-free fetal DNA (cffDNA)...

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Liquid biopsy

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of cell-free DNA Cancer screening#Blood tests Circulating free DNA Alix-Panabières, Catherine; Pantel, Klaus (January 2013). "Circulating tumor cells: liquid...

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Nanofiber

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solid tumor biopsy. This is simply a blood draw that contains circulating tumor cells (CTCs) which are shed into the bloodstream from solid tumors. Patients...

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Microvesicle

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inhibits T-cell proliferation and prevents the removal of circulating tumor cells (CTCs). As a consequence, tumor cells can turn off T-cell responses or...

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Fluorescence in situ hybridization

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cells, circulating tumor cells, and tissue samples. In this context, it can help define the spatial-temporal patterns of gene expression within cells...

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Tumor necrosis factor

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Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is a cytokine and member of the TNF superfamily...

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but less aggressive tumors composed of more mature neural cells include ganglioneuroblastoma and ganglioneuroma. Neuroblastic tumors often produce elevated...

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The tumor microenvironment is a complex ecosystem surrounding a tumor, composed of cancer cells, stromal tissue (including blood vessels, immune cells, fibroblasts...

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Mouse models of breast cancer metastasis

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Norton, L; Massagué, J (2009). "Tumor self-seeding by circulating cancer cells". Cell. 139 (7): 1315–26. doi:10.1016/j.cell.2009.11.025. PMC 2810531. PMID 20064377...

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ISET Test

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Test (Isolation by SizE of Tumor cells / Trophoblastic cells) is a diagnostic blood test that detects circulating tumor cells in a blood sample. The test...

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CTC

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halomethane Centralized traffic control, a form of railway signalling Circulating tumor cell, in the blood Closed timelike curve, in general relativity Common...

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Disseminated disease

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tumor, cancer cells circulate throughout the body. They are known as circulating tumor cells once they are in the blood. Few circulating tumor cells can disseminate to...

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Lymphocyte

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meaning cell). Lymphocytes make up between 18% and 42% of circulating white blood cells. The three major types of lymphocyte are T cells, B cells and natural...

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In situ hybridization

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Drosophila embryos), in the entire tissue (whole mount ISH), in cells, and in circulating tumor cells (CTCs). This is distinct from immunohistochemistry, which...

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Brain tumor

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A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant (cancerous) tumors and benign (non-cancerous)...

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Cancer biomarker

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markers include circulating tumor cells (CTCs) and circulating miRNAs. Both these markers are associated with the number of tumor cells present in the...

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Natural killer cell

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lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the...

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White blood cell

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classified as T cells, B cells, and natural killer cells. Neutrophils are the most abundant white blood cell, constituting 60-70% of the circulating leukocytes...

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Circulating mitochondrial DNA

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Circulating mitochondrial DNA, also called cell-free circulating mitochondrial DNA and circulating cell-free mitochondrial DNA (ccf mtDNA), are short...

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Angiogenesis

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substantial shedding of tumor cells into the vasculature, possibly contributing to the appearance of circulating tumor cells in the peripheral blood of...

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CAR T cell

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therapy). The CAR programs the T cells to target an antigen present on the tumor cell surface. For safety, CAR T cells are engineered to be specific to...

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