Cell from a primary tumor carried by blood circulation
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.
^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.
^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.
^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.
^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.
^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.
^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.
^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.
^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.
^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.
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of cell-free circulatingtumor DNA (cfDNA) has an advantage over circulatingtumorcells assays in that there is approximately 100 times more cell-free...
invasion to a second site for tumorigenesis. Some cancer cells known as circulatingtumorcells acquire the ability to penetrate the walls of lymphatic...
forms of DNA freely circulating in body fluids, including circulatingtumor DNA (ctDNA), cell-free mitochondrial DNA (ccf mtDNA), cell-free fetal DNA (cffDNA)...
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substantial shedding of tumorcells into the vasculature, possibly contributing to the appearance of circulatingtumorcells in the peripheral blood of...
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