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01.12.2015 | short review

Clinical relevance of circulating tumor cells in cancer patients

verfasst von: a.o. Prof. Dr. Gerhard Hamilton

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 4/2015

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Abstract

Historically disseminated tumor cells in solid cancers were detected by immunohistochemistry of bone marrow aspirates. Blood samples are more easily and frequently accessible and are therefore employed to detect circulating tumor cells (CTCs), a procedure termed “liquid biopsy”. CTCs are shed from tumors and a fraction of these cells is capable of establishing distal lesions. Since patients die from metastatic disease, CTCs hold potential to have prognostic significance and to indicate the success or failure of therapeutic interventions. With few exceptions, CTCs are rare cells against a large background of blood cells and need to be enriched for detection and characterization. The FDA-approved CellSearch© system relies on the selection of epithelial cell adhesion molecule (EpCAM)-positive tumor cells and is incorporated in numerous clinical studies for risk stratification and assessment of therapy. However, CTCs may have undergone (partial) epithelial-mesenchymal transition and are therefore missed by methods dependent on epithelial markers. A host of other techniques to enrich/isolate CTCs which are based on physical and/or distinct biological properties are under evaluation. Although single CTCs were linked to an increased risk of tumor progression, the actual phenotype and fraction of these cells capable of forming metastases are not known, as well as the mechanisms and kinetics of tumor cell shedding and evasion. Despite considerable progress, CTC detection methods still need to be validated and their clinical significance confirmed in larger multicenter trials before entering clinical routine practice.
Literatur
1.
Zurück zum Zitat Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer. 2006;6:449–58.PubMedCrossRef Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer. 2006;6:449–58.PubMedCrossRef
4.
Zurück zum Zitat Nelson NJ. Circulating tumor cells: will they be clinically useful? J Natl Cancer Inst. 2010;102(3):146–8.PubMedCrossRef Nelson NJ. Circulating tumor cells: will they be clinically useful? J Natl Cancer Inst. 2010;102(3):146–8.PubMedCrossRef
5.
Zurück zum Zitat Yap TA, Lorente D, Omlin A, et al. Circulating tumor cells: a multifunctional biomarker. Clin Cancer Res. 2014;20:2553–68.PubMedCrossRef Yap TA, Lorente D, Omlin A, et al. Circulating tumor cells: a multifunctional biomarker. Clin Cancer Res. 2014;20:2553–68.PubMedCrossRef
6.
Zurück zum Zitat Yu M, Bardia A, Wittner BS, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013;339:580–4.PubMedPubMedCentralCrossRef Yu M, Bardia A, Wittner BS, et al. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science. 2013;339:580–4.PubMedPubMedCentralCrossRef
7.
Zurück zum Zitat Meng S, Tripathy D, Frenkel EP, et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res. 2004;10:8152–62.PubMedCrossRef Meng S, Tripathy D, Frenkel EP, et al. Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res. 2004;10:8152–62.PubMedCrossRef
8.
Zurück zum Zitat Stott SL, Lee RJ, Nagrath S, et al. Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. Sci Transl Med. 2010;2:25ra23.PubMedPubMedCentral Stott SL, Lee RJ, Nagrath S, et al. Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer. Sci Transl Med. 2010;2:25ra23.PubMedPubMedCentral
9.
Zurück zum Zitat Camara O, Kavallaris A, Nöschel H, et al. Seeding of epithelial cells into circulation during surgery for breast cancer: the fate of malignant and benign mobilized cells. World J Surg Oncol. 2006;4:67.PubMedPubMedCentralCrossRef Camara O, Kavallaris A, Nöschel H, et al. Seeding of epithelial cells into circulation during surgery for breast cancer: the fate of malignant and benign mobilized cells. World J Surg Oncol. 2006;4:67.PubMedPubMedCentralCrossRef
10.
Zurück zum Zitat Beije N, Jager A, Sleijfer S. Circulating tumor cell enumeration by the CellSearch system: the clinician’s guide to breast cancer treatment? Cancer Treat Rev. 2015;41:144–50.PubMedCrossRef Beije N, Jager A, Sleijfer S. Circulating tumor cell enumeration by the CellSearch system: the clinician’s guide to breast cancer treatment? Cancer Treat Rev. 2015;41:144–50.PubMedCrossRef
11.
Zurück zum Zitat Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.PubMedCrossRef Cristofanilli M, Budd GT, Ellis MJ, et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004;351:781–91.PubMedCrossRef
12.
Zurück zum Zitat Ilie M, Hofman V, Long-Mira E, et al. “Sentinel” circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease. PLoS One. 2014;9:e111597.PubMedPubMedCentralCrossRef Ilie M, Hofman V, Long-Mira E, et al. “Sentinel” circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease. PLoS One. 2014;9:e111597.PubMedPubMedCentralCrossRef
13.
Zurück zum Zitat Bidard FC, Peeters DJ, Fehm T, et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 2014;15(4):406–14.PubMedCrossRef Bidard FC, Peeters DJ, Fehm T, et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 2014;15(4):406–14.PubMedCrossRef
14.
Zurück zum Zitat Marrinucci D, Bethel K, Kolatkar A, et al. Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers. Phys Biol. 2012;9:016003.PubMedPubMedCentralCrossRef Marrinucci D, Bethel K, Kolatkar A, et al. Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers. Phys Biol. 2012;9:016003.PubMedPubMedCentralCrossRef
15.
Zurück zum Zitat Friedlander TW, Fong L. The end of the beginning: circulating tumor cells as a biomarker in castration-resistant prostate cancer. J Clin Oncol. 2014;32:1104–6.PubMedCrossRef Friedlander TW, Fong L. The end of the beginning: circulating tumor cells as a biomarker in castration-resistant prostate cancer. J Clin Oncol. 2014;32:1104–6.PubMedCrossRef
16.
Zurück zum Zitat Raimondi C, Gradilone A, Naso G, et al. Clinical utility of circulating tumor cell counting through CellSearch(®): the dilemma of a concept suspended in Limbo. Onco Targets Ther. 2014;7:619–25.PubMedPubMedCentral Raimondi C, Gradilone A, Naso G, et al. Clinical utility of circulating tumor cell counting through CellSearch(®): the dilemma of a concept suspended in Limbo. Onco Targets Ther. 2014;7:619–25.PubMedPubMedCentral
17.
Zurück zum Zitat Giuliano M, Giordano A, Jackson S, et al. Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination. Breast Cancer Res. 2014;16:440.PubMedPubMedCentralCrossRef Giuliano M, Giordano A, Jackson S, et al. Circulating tumor cells as early predictors of metastatic spread in breast cancer patients with limited metastatic dissemination. Breast Cancer Res. 2014;16:440.PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat Rack B, Schindlbeck C, Jückstock J, et al. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst. 2014;106. pii: dju066.PubMedPubMedCentralCrossRef Rack B, Schindlbeck C, Jückstock J, et al. Circulating tumor cells predict survival in early average-to-high risk breast cancer patients. J Natl Cancer Inst. 2014;106. pii: dju066.PubMedPubMedCentralCrossRef
19.
Zurück zum Zitat Cohen SJ, Punt CJ, Iannotti N, 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. 2008;26:3213–21.PubMedCrossRef Cohen SJ, Punt CJ, Iannotti N, 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. 2008;26:3213–21.PubMedCrossRef
20.
Zurück zum Zitat Okegawa T, Nutahara K, Higashihara E. Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. J Urol. 2009;181:1091–7.PubMedCrossRef Okegawa T, Nutahara K, Higashihara E. Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. J Urol. 2009;181:1091–7.PubMedCrossRef
21.
Zurück zum Zitat Liberko M, Kolostova K, Bobek V. Essentials of circulating tumor cells for clinical research and practice. Crit Rev Oncol Hematol. 2013;88:338–56.PubMedCrossRef Liberko M, Kolostova K, Bobek V. Essentials of circulating tumor cells for clinical research and practice. Crit Rev Oncol Hematol. 2013;88:338–56.PubMedCrossRef
22.
23.
Zurück zum Zitat Martin M, Custodio S, de Las Casas ML, et al. Circulating tumor cells following first chemotherapy cycle: an early and strong predictor of outcome in patients with metastatic breast cancer. Oncologist. 2013;18:917–23.PubMedPubMedCentralCrossRef Martin M, Custodio S, de Las Casas ML, et al. Circulating tumor cells following first chemotherapy cycle: an early and strong predictor of outcome in patients with metastatic breast cancer. Oncologist. 2013;18:917–23.PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Liu MC, Shields PG, Warren RD, et al. Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol. 2009;27:5153–9.PubMedCrossRef Liu MC, Shields PG, Warren RD, et al. Circulating tumor cells: a useful predictor of treatment efficacy in metastatic breast cancer. J Clin Oncol. 2009;27:5153–9.PubMedCrossRef
25.
Zurück zum Zitat Truini A, Alama A, Dal Bello MG, et al. Clinical applications of circulating tumor cells in lung cancer patients by cell search system. Front Oncol. 2014;4:242.PubMedPubMedCentralCrossRef Truini A, Alama A, Dal Bello MG, et al. Clinical applications of circulating tumor cells in lung cancer patients by cell search system. Front Oncol. 2014;4:242.PubMedPubMedCentralCrossRef
26.
Zurück zum Zitat Tseng JY, Yang CY, Liang SC, Liu RS, Jiang JK, Lin CH. Dynamic changes in numbers and properties of circulating tumor cells and their potential applications. Cancers (Basel). 2014;6:2369–86.CrossRef Tseng JY, Yang CY, Liang SC, Liu RS, Jiang JK, Lin CH. Dynamic changes in numbers and properties of circulating tumor cells and their potential applications. Cancers (Basel). 2014;6:2369–86.CrossRef
28.
Zurück zum Zitat Hamilton G, Rath B, Burghuber O. Chitinase-3-like-1/YKL-40 as marker of circulating tumor cells. Transl Lung Cancer Res. 2015;4:287– 91.PubMedPubMedCentral Hamilton G, Rath B, Burghuber O. Chitinase-3-like-1/YKL-40 as marker of circulating tumor cells. Transl Lung Cancer Res. 2015;4:287– 91.PubMedPubMedCentral
29.
Zurück zum Zitat Toss A, Mu Z, Fernandez S, et al. CTC enumeration and characterization: moving toward personalized medicine. Ann Transl Med. 2014;2:108.PubMedPubMedCentral Toss A, Mu Z, Fernandez S, et al. CTC enumeration and characterization: moving toward personalized medicine. Ann Transl Med. 2014;2:108.PubMedPubMedCentral
30.
Zurück zum Zitat Dobrila-Dintinjana R. Circulating cancer cells are potential weapon for future generations. Hepatogastroenterology. 2014;61:5–8.PubMed Dobrila-Dintinjana R. Circulating cancer cells are potential weapon for future generations. Hepatogastroenterology. 2014;61:5–8.PubMed
Metadaten
Titel
Clinical relevance of circulating tumor cells in cancer patients
verfasst von
a.o. Prof. Dr. Gerhard Hamilton
Publikationsdatum
01.12.2015
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 4/2015
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-015-0237-1

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