Improving pancreatic cancer diagnosis using circulating tumor cells: prospects for staging and single-cell analysis

Court, Colin M.; Ankeny, Jacob S.; Hou, Shuang; Tseng, Hsian‐Rong; Tomlinson, James S.

doi:10.1586/14737159.2015.1091311

Cited by 40 publications

(37 citation statements)

References 77 publications

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“…Our median CTC count for PDAC patients was 2 (IQR 1–6), lower than that found using other techniques such as filters or flow cytometry. 16,20–22 One possibility is that our use of only 4 mL of VB may be too low to accurately establish the number of CTCs, especially in early-stage patients. In future studies we will assess the utility of larger blood volumes.…”

Section: Discussionmentioning

confidence: 99%

Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer

et al. 2018

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Background Occult metastatic tumors, below imaging thresholds, are a limitation of staging systems that rely on cross-sectional imaging alone and are a cause of the routine understaging of pancreatic ductal adenocarcinomas (PDACs). We investigated circulating tumor cells (CTCs) as a preoperative predictor of occult metastatic disease and as a prognostic biomarker for PDAC patients. Experimental Design A total of 126 patients (100 with cancer, 26 with benign disease) were enrolled in our study and CTCs were identified and enumerated from 4 mL of venous blood using the microfluidic NanoVelcro assay. CTC enumeration was correlated with clinicopathologic variables and outcomes following both surgical and systemic therapies. Results CTCs were identified in 78% of PDAC patients and CTC counts correlated with increasing stage (ρ = 0.42, ρ < 0.001). Of the 53 patients taken for potentially curative surgery, 13 (24.5%) had occult metastatic disease intraoperatively. Patients with occult disease had significantly more CTCs than patients with local disease only (median 7 vs. 1 CTC, p < 0.0001). At a cutoff of three or more CTCs/4 mL, CTCs correctly identified patients with occult metastatic disease preoperatively (area under the receiver operating characteristic curve 0.82, 95% confidence interval (CI) 0.76–0.98, p < 0.0001). CTCs were a univariate predictor of recurrence-free survival following surgery [hazard ratio (HR) 2.36, 95% CI 1.17–4.78, p = 0.017], as well as an independent predictor of overall survival on multivariate analysis (HR 1.38, 95% CI 1.01–1.88, p = 0.040). Conclusions CTCs show promise as a prognostic biomarker for PDAC patients at all stages of disease being treated both medically and surgically. Furthermore, CTCs demonstrate potential as a preoperative biomarker for identifying patients at high risk of occult metastatic disease.

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Section: Discussionmentioning

confidence: 99%

Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer

et al. 2018

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“…Biomimetic niches: biomaterial-based approaches to study cancer cell interactions with perturbed environment mimicking premetastatic niches (Aguado et al, 2018) Secondary metastasis 1. Staging analyses by genomics: understanding tumor subtypes and staging by genomic profiling in comparison to histological profiling (Court et al, 2015;Enokida et al, 2005;Goldsmith et al, 2019;Villani et al, 2017) 2. Single-cell-seq, metabolomics, and genomics: characterization of the metastatic nodes at multiple granularities and scale can reveal the evolution of secondary node formation (Enokida et al, 2005;Goldsmith et al, 2019) 3.…”

Section: Mechanistic Models Of Metastasis--toward Linking Mechanisms mentioning

confidence: 99%

Systems Biology of Cancer Metastasis

et al. 2019

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Cancer metastasis is no longer viewed as a linear cascade of events but rather as a series of concurrent, partially overlapping processes, as successfully metastasizing cells assume new phenotypes while jettisoning older behaviors. The lack of a systemic understanding of this complex phenomenon has limited progress in developing treatments for metastatic disease. Because metastasis has traditionally been investigated in distinct physiological compartments, the integration of these complex and interlinked aspects remains a challenge for both systems-level experimental and computational modeling of metastasis. Here, we present some of the current perspectives on the complexity of cancer metastasis, the multiscale nature of its progression, and a systems-level view of the processes underlying the invasive spread of cancer cells. We also highlight the gaps in our current understanding of cancer metastasis as well as insights emerging from interdisciplinary systems biology approaches to understand this complex phenomenon.

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“…CECs were morphologically similar between patients with PDAC, and benign and premalignant lesions, and did not confer worse prognosis in those with PDAC 89. The utility of using the presence of CTCs as a diagnostic tool is diminished by their rarity in PDAC; they are only found in 50% of cases, and are found even less often in early-stage cases 90. Consensus on appropriate phenotypic markers, including cell surface antigens and cell size, in the context of circulating leukocytes is lacking.…”

Section: Circulating Tumor Cellsmentioning

confidence: 90%

Biomarkers in pancreatic adenocarcinoma: current perspectives

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et al. 2016

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Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC.

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Improving pancreatic cancer diagnosis using circulating tumor cells: prospects for staging and single-cell analysis

Cited by 40 publications

References 77 publications

Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer

Circulating Tumor Cells Predict Occult Metastatic Disease and Prognosis in Pancreatic Cancer

Systems Biology of Cancer Metastasis

Biomarkers in pancreatic adenocarcinoma: current perspectives

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