Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance

Sun, Yun-Fan; Yang, Xin‐Rong; Zhou, Jian; Qiu, Shuang–Jian; Fan, Jia; Xu, Yang

doi:10.1007/s00432-011-0988-y

Cited by 163 publications

(141 citation statements)

References 150 publications

(148 reference statements)

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“…Therefore, DLA provides an upper estimate for minimal residual disease (MRD) in the circulation, comprising usually less than 10,000 CTCs per patient, and we deem it unlikely that CTC numbers are several-fold higher. Whether CTCs increase on average 100-fold in M1-stage patients, as suggested by other approaches (22,23), needs to be explored. Among our patients, M1-stage patients harbored about 10-fold more CTCs than M0-stage patients.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients

Fischer

Niederacher²,

Topp

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

189

198

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Significance The infrequent detection of circulating tumor cells (CTCs) has hindered their clinical implication and their potential use in the sense of a “liquid biopsy” for cancer diagnosis and therapy. Hypothesizing that the limited blood volume commonly used for CTC analysis (1–10 mL) accounts for variable detection rates, we used leukapheresis to screen large blood volumes for CTCs. This enabled a more reliable detection of CTCs at high frequency even in nonmetastatic cancer patients. Thus, diagnostic leukapheresis may facilitate the routine clinical use of CTCs as biomarkers for personalized medicine. Combined with technologies for single-cell molecular genetics or cell biology, it may significantly improve prediction of therapy response and monitoring, especially in early systemic cancer.

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Section: Discussionmentioning

confidence: 99%

Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients

Fischer

Niederacher²,

Topp

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

189

198

View full text Add to dashboard Cite

show abstract

“…Circulating tumor cells (CTC) can readily be detected in almost all human malignant diseases and carry the potential to become metastatic cells [33][34][35]. Importantly, they can be detected with a relatively high incidence even in early stage disease [34].…”

Section: Circulating Cancer Cellsmentioning

confidence: 99%

“…Importantly, they can be detected with a relatively high incidence even in early stage disease [34]. Reports on the comparison of early and late stage disease CTC numbers found limited correlation [36,37].…”

Section: Circulating Cancer Cellsmentioning

confidence: 99%

“…However, this calculation must be corrected with the share of blood flow of the individual metastatic organ. In case of the skin, the 5 % means 1/20 of the entire blood volume, meaning that 20 times more CTC is necessary to produce 1 single skin colony (equivalent of 250-500 CTC/10 ml), a very high number that is rarely detected in humans [33][34][35]. Due to the aforementioned obstacles in the skin microenvironment and the low perfusion rate, the colonization of the skin requires a rather high CTC number that occurs only in a limited number of cancer cases and in general at late stages.…”

Section: Circulating Cancer Cellsmentioning

confidence: 99%

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Tumor type-specific and skin region-selective metastasis of human cancers: another example of the “seed and soil” hypothesis

Kovács

Hegedűs

Kenessey

et al. 2013

Cancer Metastasis Rev

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Metastasis of human cancer is an organ-selective process that is determined by anatomical and biological factors as well as by specific microenvironmental properties. Dissemination of visceral malignancies to the skin is rather rare and usually occurs in a later stage of the disease. Using statistical approaches, both positive (renal and lung cancers) and negative (pancreatic and liver cancers) organ preferences can be identified in a variety of cancers. While certain cancer types are characterized by random distribution for skin metastasis (liver cancer), a number of cancers demonstrate a colonization preference to the region of origin: lung cancer to the supradiaphragmatic (mostly chest) and colorectal cancers to the infradiaphragmatic (abdominal) skin regions. In certain cases, however, skin metastasis develops more frequently at specific distant locations, as evidenced by the dissemination of renal cancer at the head and neck region. These findings are clinically relevant and useful especially in patients where skin metastasis is the first indication of a malignancy. Nevertheless, it is a strong argument for the predominant role of microenvironmental factors in cancer dissemination. On the other hand, skin metastases of visceral cancers provide a unique model to analyze the pathomechanisms determining organ selectivity, including the organ-specific vascularization, the dermatome-specific innervation, or immunological and developmental factors.

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“…CTC are generally isolated from primary tumors or metastatic sites and these cells flow in the bloodstream of patients with malignancies 11. To date, CTC have been focused on as a target for detecting occult tumors, predicting therapeutic responses and prognoses, and monitoring postoperative recurrence in the clinical management of patients with various malignancies, including gastric cancer 12, 13. Non‐invasive liquid biopsy has enabled CTC to be characterized and their numbers assessed.…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of circulating tumor cells in blood from patients with gastric cancer

Arigami

Uenosono

Yanagita

et al. 2017

Annals of Gastroent Surgery

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Circulating tumor cells (CTC) have been focused on as a target for detecting occult tumors, predicting therapeutic responses and prognoses, and monitoring postoperative recurrence in the clinical management of patients with various malignancies, including gastric cancer. Recent advances in molecular diagnostic tools have contributed to high sensitivity and specificity for the detection of CTC. A conspicuous disparity exists in the incidence of CTC among studies. However, a close relationship has been reported between positivity for CTC and well‐known prognostic clinicopathological factors including depth of tumor invasion, lymph node metastasis, stage, and lymphatic and venous invasion in patients with gastric cancer. According to most studies published on the clinical impact of CTC, the presence of CTC negatively affects the prognosis of patients with gastric cancer. Moreover, the study of CTC based on a meta‐analysis demonstrated their importance as a poor prognostic indicator. In clinical management, pre‐ and post‐therapeutic monitoring of CTC using liquid biopsy may be useful for early detection of subclinical patients or disease recurrence, prediction of tumor progression, and administrative control of adjuvant chemotherapy. Although their functional properties remain unclear, molecular profiling of CTC may contribute to the development of personalized treatment that effectively inhibits tumor progression in patients with advanced gastric cancer. We herein review the clinical significance of CTC as a promising blood marker and therapeutic target in patients with gastric cancer.

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Circulating tumor cells: advances in detection methods, biological issues, and clinical relevance

Abstract: This review addresses the majority of assays that have been published thus far, including the enrichment and detection steps and the markers used in these assays, accompanied by some biological issues of CTC and the results of clinical application harvested.

Cited by 163 publications

References 150 publications

Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients

Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients

Tumor type-specific and skin region-selective metastasis of human cancers: another example of the “seed and soil” hypothesis

Clinical significance of circulating tumor cells in blood from patients with gastric cancer

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