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Circulating Tumor Cells
Circulating Tumor Cells
Circulating Tumor Cells
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• Free DNA and, to a lesser extent, RNA circulating in plasma from patients
with cancer have been described
• Origin of these nucleic acids may also include direct shedding from
necrotic cells in tumor deposits, tumor-derived exosomes, or cellular
fragments or lysis of CTCs in the bloodstream
• Some approaches have focused on isolating nucleic acids directly from
cell-free plasma
(Yu et al, 2011)
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Micrographs of CTCs
Combined fluorescent and reflected light micrographs of a cytokeratin 7/8 (green) stained CTC captured
from breast cancer patient blood and a contaminating CD45-positive (red) white blood cell (A) and
cytokeratin 7/8 (green, B) and PSA (green, C) stained CTCs captured from a prostate cancer patient
(D and E) HER2 (green, D) and cytokeratin 7/8 (green, E) stained CTCs captured from a breast cancer
patient. In all panels, the nuclei are stained with DAPI (4',6-diamidino-2-phenylindole) (blue)
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Micrographs of CTCs
(F and G) Individual and merged fluorescent micrographs of CTCs captured from prostate cancer
patients’ blood stained positive for PSA (green) and Ki-67 (red) (F), and PSA (green) and M30 (red,
apoptotic marker) (G)
In all panels, the nuclei are stained with DAPI (4',6-diamidino-2-phenylindole) (blue)
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In patients with metastatic breast cancer, CTC counts above five CTCs per 7.5
ml of blood before the start of systemic therapy were associated with a shorter
median progression-free survival and overall survival(Botteri et al, 2010)
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• CTCs can be used to test for molecular evolution of tumors during the
course of treatment
• Some HER2-positive CTCs are reported in breast cancer patients
whose primary tumor was HER2 negative (Meng et al., 2004; Wülfing
et al., 2006)
• As well as some HER2-negative CTCs emerging in HER2-positive
breast cancers subjected to anti-HER2 therapy (Hayes et al., 2002).
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Future perspectives
• The molecular characterization of CTCs has the potential to revolutionize
understanding of cancer metastasis
• Technological platforms highly sensitive and reliable CTC isolation
• As the technology evolves further, a broad range of potential applications
can be applied
• the noninvasive monitoring of tumor genotypes to the identification
and analysis of metastatic precursor cell subpopulations
• early detection of invasive but localized cancer
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References
• Adams DL, Zhu P, Makarova OV, Martin SS, Charpentier M,
Chumsri S and Tang CM. (2014). The systematic study of circulating
tumor cell isolation using lithographic microfilters. RSC Advances; 9,
4334–4342.
• Danila DC, Pantel K, Fleisher M, and Scher HI. (2011) Circulating
Tumors Cells as Biomarkers: Progress Toward Biomarker
Qualification. Cancer Journal; 17(6), 438–450.
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References
• Hayes DF, Walker TM, Singh B, Vitetta ES, Uhr JW, Gross S, Rao C,
Doyle GV, and Terstappen LW. 2002. Monitoring expression of HER-
2 on circulating epithelial cells in patients with advanced breast
cancer. Int.J. Oncol; 21:1111–1117.
• Maheswaran S, Sequist LV, Nagrath S, Ulkus K, Brannigan B,
Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW. (2008)
Detection of mutations in EGFR in circulating lung-cancer cells. N.
Engl. J. Med. 359:366–377
References
• Meng, S, Tripathy D, Shete S, Ashfaq R, Haley B, Perkins S, Beitsch
P, Khan A, Euhus D, Osborne C, et al. 2004. HER-2 gene
amplification can be acquired as breast cancer progresses. Proc. Natl.
Acad. Sci; 101:9393–9398
• Pachmann K, Camara O, Kavallaris A, Schneider U, Schünemann S,
and Höffken K. (2005) Quantification of the response of circulating
epithelial cells to neodadjuvant treatment for breast cancer: a new
tool for therapy monitoring. Breast Cancer Res. 7:975–979
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References
• Wülfing P, Borchard J, Buerger H, Heidl S, Zänker KS, Kiesel L and
Brandt B. (2006) HER2-positive circulating tumor cells indicate poor
clinical outcome in stage I to III breast cancer patients. Clin. Cancer
Res;12:1715–1720
• Yu M, Stott S, Toner M, Maheswaran S, and Daniel A. (2011)
Circulating tumor cells: approaches to isolation and characterization.
J. Cell boil; 192(3): 373-382.
Thank You!
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