Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology

Kruspe, Sven; Dickey, David D.; Urak, Kevin T.; Blanco, Giselle N.; Miller, Matthew J.; Clark, Karen C; Burghardt, Elliot; Gutierrez, Wade R.; Phadke, Sneha; Kamboj, Sukriti; Ginader, Timothy; Smith, Brian J.; Grimm, Sarah K.; Schappet, James; Ozer, Howard; Thomas, Alexandra; McNamara, James O; Chan, Carlos; Giangrande, Paloma H.

doi:10.1016/j.omtn.2017.08.004

Cited by 31 publications

(30 citation statements)

References 65 publications

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“…This study used CTC‐derived nucleases for signal amplification, as these enzymes are elevated in many cancers including EMT‐induced breast cancers. The researchers concluded that fluorescent nuclease‐activated probes can be used to rapidly examine CTC levels as a method of early diagnosis in a cost‐effective manner . However, using CTC for cancer diagnosis is in its very early stages and further research should be conducted on CTC detection methods and its utilization in cancer diagnosis.…”

Section: Utilization Of Liquid Biopsy For Breast Cancer In the Clinicmentioning

confidence: 99%

Liquid biopsy in breast cancer: A comprehensive review

2019

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Breast cancer is the most common cancer among women worldwide. Due to its complexity in nature, effective breast cancer treatment can encounter many challenges. Traditional methods of cancer detection such as tissue biopsy are not comprehensive enough to capture the entire genomic landscape of breast tumors. However, with the introduction of novel techniques, the application of liquid biopsy has been enhanced, enabling the improvement of various aspects of breast cancer management including early diagnosis and screening, prediction of prognosis, early detection of relapse, serial sampling and efficient longitudinal monitoring of disease progress and response to treatment. Various components of tumor cells released into the blood circulation can be analyzed in liquid biopsy sampling, some of which include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell‐free RNA, tumor‐educated platelets and exosomes. These components can be utilized for different purposes. As an example, ctDNA can be sequenced for genetic profiling of the tumors to enhance individualized treatment and longitudinal screening. CTC plasma count analysis or ctDNA detection after curative tumor resection surgery could facilitate early detection of minimal residual disease, aiding in the initiation of adjuvant therapy to prevent recurrence. Furthermore, CTC plasma count can be assessed to determine the stage and prognosis of breast cancer. In this review, we discuss the advantages and limitations of the various components of liquid biopsy used in breast cancer diagnosis and will expand on aspects that require further focus in future research.

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Section: Utilization Of Liquid Biopsy For Breast Cancer In the Clinicmentioning

confidence: 99%

Liquid biopsy in breast cancer: A comprehensive review

2019

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“…Second, rising mutant KRAS ctDNA during postoperative follow-up anticipates radiographic/clinical recurrence 38 . Current studies have demonstrated potential clinical applicability in longitudinal monitoring of PDAC subjects to provide predictive and prognostic information that was relevant to therapeutic decisions 39 , while others have shown that CTC-derived nucleases can be exploited for signal amplification in detection methods 40 . P-AscH − decreases CTC-derived nucleases in subjects with stage 4 metastatic PDAC while P-AscH − treatment had little effect on CTC-derived nucleases in patients with loco-regional PDAC without distant metastases.…”

Section: Discussionmentioning

confidence: 99%

“…The CTC-derived nuclease activity assay was performed as previously described 40 . Plasma samples were collected from subjects with stage 4 metastatic pancreatic cancer enrolled in a phase I trial where P-AscH − was combined with gemcitabine 7 approved by The University of Iowa Human Institutional Review Board and the Protocol Review and Monitoring Committee of the Holden Comprehensive Cancer Center at The University of Iowa Hospitals and Clinics on May 22, 2008.…”

Section: Methodsmentioning

confidence: 99%

Pharmacological ascorbate inhibits pancreatic cancer metastases via a peroxide-mediated mechanism

O’Leary

Alexander

et al. 2020

Sci Rep

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Pharmacological ascorbate (P-AscH−, high-dose, intravenous vitamin C) is cytotoxic to tumor cells in doses achievable in humans. Phase I studies in pancreatic cancer (PDAC) utilizing P-AscH− have demonstrated increases in progression free survival, suggesting a reduction in metastatic disease burden. The purpose of this study was to determine the effects of P-AscH− on metastatic PDAC. Several in vitro and in vivo mechanisms involved in PDAC metastases were investigated following treatment with P-AscH−. Serum from PDAC patients in clinical trials with P-AscH− were tested for the presence and quantity of circulating tumor cell-derived nucleases. P-AscH− inhibited invasion, basement membrane degradation, decreased matrix metalloproteinase expression, as well as clonogenic survival and viability during exposure to fluid shear stress. In vivo, P-AscH− significantly decreased formation of ascites, tumor burden over time, circulating tumor cells, and hepatic metastases. Both in vitro and in vivo findings were reversed with the addition of catalase suggesting that the effect of P-AscH− on metastatic disease is mediated by hydrogen peroxide. Finally, P-AscH− decreased CTC-derived nucleases in subjects with stage IV PDAC in a phase I clinical trial. We conclude that P-AscH− attenuates the metastatic potential of PDAC and may prove to be effective for treating advanced disease.

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“…In these methods, blood is filtered through pores that trap molecules larger than the maximum pore sizes. ISET ® (Paris, France) [18,19], ScreenCell ® (Sarcelles, France) [20,21], CellSieve™ (Rockville, MD, USA) [22,23], Flexible Micro Spring Array (FMSA) [24], Parsortix™ (Angle PLC, Guildford, UK) [25,26], Resettable Cell Trap [27] and Cluster Chip [28] are some of the devices available on the market. Filtration does not capture CTCs with a size the same as, or smaller than, the pore diameter.…”

Section: Current Methodologies For Ctc Enrichment and Isolation: Pmentioning

confidence: 99%

Circulating Tumor Cell-Derived Pre-Clinical Models for Personalized Medicine

Gabriel

Cochonneau

Cadé

et al. 2018

Cancers

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The main cause of death from cancer is associated with the development of metastases, resulting from the inability of current therapies to cure patients at metastatic stages. Generating preclinical models to better characterize the evolution of the disease is thus of utmost importance, in order to implement effective new cancer biomarkers and therapies. Circulating Tumor Cells (CTCs) are good candidates for generating preclinical models, making it possible to follow up the spatial and temporal heterogeneity of tumor tissues. This method is a non-invasive liquid biopsy that can be obtained at any stage of the disease. It partially summarizes the molecular heterogeneity of the corresponding tumors at a given time. Here, we discuss the CTC-derived models that have been generated so far, from simplified 2D cultures to the most complex CTC-derived explants (CDX models). We highlight the challenges and strengths of these preclinical tools, as well as some of the recent studies published using these models.

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Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology

Cited by 31 publications

References 65 publications

Liquid biopsy in breast cancer: A comprehensive review

Liquid biopsy in breast cancer: A comprehensive review

Pharmacological ascorbate inhibits pancreatic cancer metastases via a peroxide-mediated mechanism

Circulating Tumor Cell-Derived Pre-Clinical Models for Personalized Medicine

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