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Daniel A. Haber - One of the best experts on this subject based on the ideXlab platform.

  • ultra fast vitrification of patient derived Circulating Tumor Cell lines
    PLOS ONE, 2018
    Co-Authors: Rebecca D Sandlin, Shyamala Maheswaran, Daniel A. Haber, Keith H K Wong, Shannon N Tessier, Anisa Swei, Lauren D Bookstaver, Bennett E Ahearn, Shannon L Stott
    Abstract:

    Emerging technologies have enabled the isolation and characterization of rare Circulating Tumor Cells (CTCs) from the blood of metastatic cancer patients. CTCs represent a non-invasive opportunity to gain information regarding the primary Tumor and recent reports suggest CTCs have value as an indicator of disease status. CTCs are fragile and difficult to expand in vitro, so typically molecular characterization must be performed immediately following isolation. To ease experimental timelines and enable biobanking, cryopreservation methods are needed. However, extensive Cellular heterogeneity and the rarity of CTCs complicates the optimization of cryopreservation methods based upon Cell type, necessitating a standardized protocol. Here, we optimized a previously reported vitrification protocol to preserve patient-derived CTC Cell lines using highly conductive silica microcapillaries to achieve ultra-fast cooling rates with low cryoprotectant concentrations. Using this vitrification protocol, five CTC Cell lines were cooled to cryogenic temperatures. Thawed CTCs exhibited high Cell viability and expanded under in vitro Cell culture conditions. EpCAM biomarker expression was maintained for each CTC Cell line. One CTC Cell line was selected for molecular characterization, revealing that RNA integrity was maintained after storage. A qPCR panel showed no significant difference in thawed CTCs compared to fresh controls. The data presented here suggests vitrification may enable the standardization of cryopreservation methods for CTCs.

  • a conduit to metastasis Circulating Tumor Cell biology
    Genes & Development, 2017
    Co-Authors: Douglas S Micalizzi, Shyamala Maheswaran, Daniel A. Haber
    Abstract:

    Advances in the enrichment and analysis of rare Cells from the bloodstream have allowed for detection and characterization of Circulating Tumor Cells (CTCs) from patients with cancer. The analysis of CTCs has provided significant insight into the metastatic process. Studies on the biology of CTCs have begun to elucidate the molecular mechanisms of CTC generation, intravasation, survival, interactions with components of the blood, extravasation, and colonization of distant organs. Additionally, the study of CTCs has exposed dramatic intrapatient and interpatient heterogeneity and their evolution over time. In this review, we focus on the current knowledge of CTC biology and the potential clinical implications.

  • Clusters of Circulating Tumor Cells: a Biophysical and Technological Perspective.
    Current opinion in biomedical engineering, 2017
    Co-Authors: Jon F Edd, Shyamala Maheswaran, Daniel A. Haber, Shannon L Stott, Mehmet Toner
    Abstract:

    The vast majority of cancer associated deaths result from metastasis, yet the behaviors of its most potent Cellular driver, Circulating Tumor Cell clusters, are only beginning to be revealed. This review highlights recent advances to our understanding of Tumor Cell clusters with emphasis on enabling technologies. The importance of interCellular adhesions among Cells in clusters have begun to be unraveled with the aid of promising microfluidic strategies for isolating clusters from patient blood. Due to their metastatic potency, the utility of Circulating Tumor Cell clusters for cancer diagnosis, drug screening, precision oncology and as targets of antimetastatic therapeutics are being explored. The continued development of tools for exploring Circulating Tumor Cell clusters will enhance our fundamental understanding of the metastatic process and may be instrumental in devising new strategies to suppress and eliminate metastasis.

  • microfluidic isolation of Circulating Tumor Cell clusters by size and asymmetry
    Scientific Reports, 2017
    Co-Authors: Jon F Edd, Shyamala Maheswaran, Daniel A. Haber, Amy E Stoddard, Keith H K Wong, Fabio Fachin, Shannon L Stott, Ravi Kapur, Mehmet Toner
    Abstract:

    Circulating Tumor Cell clusters (CTC clusters) are potent initiators of metastasis and potentially useful clinical markers for patients with cancer. Although there are numerous devices developed to isolate individual Circulating Tumor Cells from blood, these devices are ineffective at capturing CTC clusters, incapable of separating clusters from single Cells and/or cause cluster damage or dissociation during processing. The only device currently able to specifically isolate CTC clusters from single CTCs and blood Cells relies on the batch immobilization of clusters onto micropillars which necessitates long residence times and causes damage to clusters during release. Here, we present a two-stage continuous microfluidic chip that isolates and recovers viable CTC clusters from blood. This approach uses deterministic lateral displacement to sort clusters by capitalizing on two geometric properties: size and asymmetry. Cultured breast cancer CTC clusters containing between 2–100 + Cells were recovered from whole blood using this integrated two-stage device with minimal cluster dissociation, 99% recovery of large clusters, Cell viabilities over 87% and greater than five-log depletion of red blood Cells. This continuous-flow cluster chip will enable further studies examining CTC clusters in research and clinical applications.

  • en route to metastasis Circulating Tumor Cell clusters and epithelial to mesenchymal transition
    Trends in cancer, 2015
    Co-Authors: Nicola Aceto, Shyamala Maheswaran, Daniel A. Haber, Mehmet Toner
    Abstract:

    Blood-borne metastasis accounts for the vast majority of cancer-related deaths and it is fueled by the generation of Circulating Tumor Cells (CTCs) from a primary Tumor deposit. Recent technological advances have made it possible to characterize human CTCs as they travel within the bloodstream. CTCs are found both as single Cells and as clusters of Cells held together by interCellular junctions. Although less prevalent, CTC clusters appear to have greater metastatic potential than single CTCs in the circulation. Both may exhibit shifts in expression of epithelial and mesenchymal markers, which may show dynamic changes during cancer progression. In this review we discuss recent insights into the biological properties of individual and clustered cancer Cells in the circulation.

David T Miyamoto - One of the best experts on this subject based on the ideXlab platform.

  • abstract 1734 absolute quantification of Circulating Tumor Cell rna enables high specificity detection of hepatoCellular carcinoma
    Cancer Research, 2017
    Co-Authors: Mark Kalinich, David T Miyamoto, Xin Hong, Irun Bhan, Tanya T Kwan, Sarah Javaid, Joseph A Licausi, John D Milner, Lipika Goyal, Srinjoy Sil
    Abstract:

    Background: Although liver cancer has the second-highest mortality rate among cancers internationally, accurate and scalable assays for the early detection and longitudinal monitoring of hepatoCellular carcinoma are lacking. Circulating Tumor Cells are released from invasive cancers into the blood stream, but the difficulty inherent in isolating, identifying, and characterizing these ultra-rare Cells has precluded their widespread implementation as a biomarker. By combining a high-throughput microfluidic negative depletion CTC isolation strategy with the absolute quantification of lineage-specific RNAs, we report the highly specific detection of hepatoCellular carcinoma CTCs from patient blood draws. Methods: Blood draws from 48 hepatoCellular carcinoma patients, 31 chronic liver disease patients, 25 healthy donors, and 44 patients with primary cancers other than hepatoCellular carcinoma were processed through the microfluidic device (CTC-iChip). RNA was extracted, whole-transcriptome amplified, and quantified using droplet digital PCR. Transcript counts were used to fit a logistic regression model to integrate distinct transcript levels into a single CTC-score. The technical feasibility of utilizing RNA sequencing for identification of novel CTC transcripts of interest was also demonstrated with a liver cancer Cell line spike-in study. Results: 9 of the 16 untreated HCC patients were successfully detected, while only 1/31 chronic liver disease patients were incorrectly classified. HCC patients undergoing treatment showed a significant decrease in their CTC-score; only 9/32 patients actively receiving treatment were positive. The CTC-score was not correlated with the HCC serum biomarker alpha-fetoprotein, and combining these two orthogonal measures led to estimated positive and negative predictive values of 80% and 86%, respectively, in a high-risk cohort. RNAseq analysis of Cell line spike-in data revealed the potential of RNA sequencing for uncovering novel transcripts of interest. Conclusion: Coupling microfluidic depletion with droplet digital PCR allows for the highly specific detection of hepatoCellular carcinoma. The CTC-score generated from these data tracks with clinical intervention and is orthogonal to the existing biomarker AFP; combining these two assays has the potential to provide superior detection compared to either individual approach. Citation Format: Mark Kalinich, Irun Bhan, Tanya T. Kwan, David T. Miyamoto, Sarah Javaid, Joseph A. LiCausi, John D. Milner, Xin Hong, Lipika Goyal, Srinjoy Sil, Melissa Choz, Ravi Kapur, Alona Muzikansky, Huidan Zhang, David A. Weitz, Lecia V. Sequist, David P. Ryan, Raymond Chung, Andrew X. Zhu, Kurt J. Isselbacher, David T. Ting, Mehmet Toner, Shyamala Maheswaran, Daniel A. Haber. Absolute quantification of Circulating Tumor Cell RNA enables high specificity detection of hepatoCellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1734. doi:10.1158/1538-7445.AM2017-1734

  • abstract 1736 a novel rna based assay for the detection and monitoring of Circulating Tumor Cell signatures in breast cancer
    Cancer Research, 2017
    Co-Authors: Tanya T Kwan, Tilak Sundaresan, David T Miyamoto, Aditya Bardia, Xin Hong, Mark Kalinich, Sarah Javaid, Joseph A Licausi, Laura Spring, Erin Silva
    Abstract:

    Examination of Circulating Tumor Cells (CTCs) holds the potential of offering a real-time non-invasive window into Tumor biology. Information gleaned from CTC detection and characterization can be used for early cancer detection, choice of therapy decisions and long-term monitoring for disease recurrence and the emergence of drug resistance mechanisms. However, technical difficulties with CTC isolation and the inherent limitations of imaging-based analysis have hindered the broad clinical use of CTCs as biomarkers. To overcome these concerns, we have combined our unbiased microfluidic CTC enrichment technology, the iChip, with a highly sensitive and specific multi-gene RNA-based biomarker panel to develop an assay that detects CTC signatures in patient blood samples in a high throughput and quantitative fashion. This assay was applied to a cohort of breast cancer patients, including women with both localized and metastatic disease. It successfully identified CTC signal in 50-70% of metastatic and 20-40% of localized pretreatment patient samples. Patient CTC scores, assigned based on a multi-marker prediction algorithm, correlated with cancer stage and grade, but not with hormone receptor status, suggesting the applicability of the assay to a wide range of breast cancer subtypes. To determine if CTC scoring was useful for disease monitoring, we performed monthly blood collection from metastatic patients starting a new line of treatment. CTC score as early as one month after initiation of therapy, but not at pretreatment, was predictive of progression-free survival and treatment outcome, suggesting that real-time kinetic changes in CTC signatures are more clinically informative that one-time static evaluation of their presence in a given sample. In addition, a subset of high-risk genes showed expression patterns over the course of treatment that highly correlated with disease recurrence. This observation indicates that a multi-marker panel can parse out dynamic changes in cancer gene expression programs and provide a molecular insight into treatment responses that are not achievable by assays built around one or few markers. In conclusion, our novel RNA-based method of identifying CTC signatures in liquid biopsies provides a sensitive platform for breast cancer detection and monitoring that goes beyond CTC enumeration. It offers a non-invasive quantitative molecular characterization of Tumor gene expression that can be used to guide informed clinical decisions in both standard course of care and clinical trial settings. Citation Format: Tanya T. Kwan, Aditya Bardia, Tilak Sundaresan, Laura Spring, Mark Kalinich, David Miyamoto, Xin Hong, Joseph LiCausi, Uyen Ho, Sarah Javaid, Erin Silva, Lecia Sequist, Shyamala Maheswaran, Daniel Haber. A novel RNA-based assay for the detection and monitoring of Circulating Tumor Cell signatures in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1736. doi:10.1158/1538-7445.AM2017-1736

  • a microfluidic device for label free physical capture of Circulating Tumor Cell clusters
    Nature Methods, 2015
    Co-Authors: Fatih A Sarioglu, Nicola Aceto, Nikola Kojic, Maria C Donaldson, Mahnaz Zeinali, Bashar Hamza, Amanda Engstrom, Tilak Sundaresan, David T Miyamoto, Aditya Bardia
    Abstract:

    The Cluster-Chip provides highly efficient and gentle capture of Circulating Tumor Cell clusters from milliliters of unprocessed whole blood, making it possible to study how these clusters contribute to metastasis.

  • A microfluidic device for label-free, physical capture of Circulating Tumor Cell clusters
    Nature Methods, 2015
    Co-Authors: A Fatih Sarioglu, Nicola Aceto, Nikola Kojic, Maria C Donaldson, Mahnaz Zeinali, Bashar Hamza, Amanda Engstrom, David T Miyamoto, Tilak K Sundaresan, Aditya Bardia
    Abstract:

    The Cluster-Chip provides highly efficient and gentle capture of Circulating Tumor Cell clusters from milliliters of unprocessed whole blood, making it possible to study how these clusters contribute to metastasis. Cancer Cells metastasize through the bloodstream either as single migratory Circulating Tumor Cells (CTCs) or as multiCellular groupings (CTC clusters). Existing technologies for CTC enrichment are designed to isolate single CTCs, and although CTC clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here we developed a microchip technology (the Cluster-Chip) to capture CTC clusters independently of Tumor-specific markers from unprocessed blood. CTC clusters are isolated through specialized bifurcating traps under low–shear stress conditions that preserve their integrity, and even two-Cell clusters are captured efficiently. Using the Cluster-Chip, we identified CTC clusters in 30–40% of patients with metastatic breast or prostate cancer or with melanoma. RNA sequencing of CTC clusters confirmed their Tumor origin and identified tissue-derived macrophages within the clusters. Efficient capture of CTC clusters will enable the detailed characterization of their biological properties and role in metastasis.

  • a microfluidic device for label free physical capture of Circulating Tumor Cell clusters
    Nature Methods, 2015
    Co-Authors: Fatih A Sarioglu, Nicola Aceto, Nikola Kojic, Maria C Donaldson, Mahnaz Zeinali, Bashar Hamza, Amanda Engstrom, Tilak Sundaresan, Huili Zhu, David T Miyamoto
    Abstract:

    Cancer Cells metastasize through the bloodstream either as single migratory Circulating Tumor Cells (CTCs) or as multiCellular groupings (CTC clusters). Existing technologies for CTC enrichment are designed to isolate single CTCs, and although CTC clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here we developed a microchip technology (the Cluster-Chip) to capture CTC clusters independently of Tumor-specific markers from unprocessed blood. CTC clusters are isolated through specialized bifurcating traps under low-shear stress conditions that preserve their integrity, and even two-Cell clusters are captured efficiently. Using the Cluster-Chip, we identified CTC clusters in 30-40% of patients with metastatic breast or prostate cancer or with melanoma. RNA sequencing of CTC clusters confirmed their Tumor origin and identified tissue-derived macrophages within the clusters. Efficient capture of CTC clusters will enable the detailed characterization of their biological properties and role in metastasis.

Aditya Bardia - One of the best experts on this subject based on the ideXlab platform.

  • abstract 1736 a novel rna based assay for the detection and monitoring of Circulating Tumor Cell signatures in breast cancer
    Cancer Research, 2017
    Co-Authors: Tanya T Kwan, Tilak Sundaresan, David T Miyamoto, Aditya Bardia, Xin Hong, Mark Kalinich, Sarah Javaid, Joseph A Licausi, Laura Spring, Erin Silva
    Abstract:

    Examination of Circulating Tumor Cells (CTCs) holds the potential of offering a real-time non-invasive window into Tumor biology. Information gleaned from CTC detection and characterization can be used for early cancer detection, choice of therapy decisions and long-term monitoring for disease recurrence and the emergence of drug resistance mechanisms. However, technical difficulties with CTC isolation and the inherent limitations of imaging-based analysis have hindered the broad clinical use of CTCs as biomarkers. To overcome these concerns, we have combined our unbiased microfluidic CTC enrichment technology, the iChip, with a highly sensitive and specific multi-gene RNA-based biomarker panel to develop an assay that detects CTC signatures in patient blood samples in a high throughput and quantitative fashion. This assay was applied to a cohort of breast cancer patients, including women with both localized and metastatic disease. It successfully identified CTC signal in 50-70% of metastatic and 20-40% of localized pretreatment patient samples. Patient CTC scores, assigned based on a multi-marker prediction algorithm, correlated with cancer stage and grade, but not with hormone receptor status, suggesting the applicability of the assay to a wide range of breast cancer subtypes. To determine if CTC scoring was useful for disease monitoring, we performed monthly blood collection from metastatic patients starting a new line of treatment. CTC score as early as one month after initiation of therapy, but not at pretreatment, was predictive of progression-free survival and treatment outcome, suggesting that real-time kinetic changes in CTC signatures are more clinically informative that one-time static evaluation of their presence in a given sample. In addition, a subset of high-risk genes showed expression patterns over the course of treatment that highly correlated with disease recurrence. This observation indicates that a multi-marker panel can parse out dynamic changes in cancer gene expression programs and provide a molecular insight into treatment responses that are not achievable by assays built around one or few markers. In conclusion, our novel RNA-based method of identifying CTC signatures in liquid biopsies provides a sensitive platform for breast cancer detection and monitoring that goes beyond CTC enumeration. It offers a non-invasive quantitative molecular characterization of Tumor gene expression that can be used to guide informed clinical decisions in both standard course of care and clinical trial settings. Citation Format: Tanya T. Kwan, Aditya Bardia, Tilak Sundaresan, Laura Spring, Mark Kalinich, David Miyamoto, Xin Hong, Joseph LiCausi, Uyen Ho, Sarah Javaid, Erin Silva, Lecia Sequist, Shyamala Maheswaran, Daniel Haber. A novel RNA-based assay for the detection and monitoring of Circulating Tumor Cell signatures in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1736. doi:10.1158/1538-7445.AM2017-1736

  • a microfluidic device for label free physical capture of Circulating Tumor Cell clusters
    Nature Methods, 2015
    Co-Authors: Fatih A Sarioglu, Nicola Aceto, Nikola Kojic, Maria C Donaldson, Mahnaz Zeinali, Bashar Hamza, Amanda Engstrom, Tilak Sundaresan, David T Miyamoto, Aditya Bardia
    Abstract:

    The Cluster-Chip provides highly efficient and gentle capture of Circulating Tumor Cell clusters from milliliters of unprocessed whole blood, making it possible to study how these clusters contribute to metastasis.

  • A microfluidic device for label-free, physical capture of Circulating Tumor Cell clusters
    Nature Methods, 2015
    Co-Authors: A Fatih Sarioglu, Nicola Aceto, Nikola Kojic, Maria C Donaldson, Mahnaz Zeinali, Bashar Hamza, Amanda Engstrom, David T Miyamoto, Tilak K Sundaresan, Aditya Bardia
    Abstract:

    The Cluster-Chip provides highly efficient and gentle capture of Circulating Tumor Cell clusters from milliliters of unprocessed whole blood, making it possible to study how these clusters contribute to metastasis. Cancer Cells metastasize through the bloodstream either as single migratory Circulating Tumor Cells (CTCs) or as multiCellular groupings (CTC clusters). Existing technologies for CTC enrichment are designed to isolate single CTCs, and although CTC clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here we developed a microchip technology (the Cluster-Chip) to capture CTC clusters independently of Tumor-specific markers from unprocessed blood. CTC clusters are isolated through specialized bifurcating traps under low–shear stress conditions that preserve their integrity, and even two-Cell clusters are captured efficiently. Using the Cluster-Chip, we identified CTC clusters in 30–40% of patients with metastatic breast or prostate cancer or with melanoma. RNA sequencing of CTC clusters confirmed their Tumor origin and identified tissue-derived macrophages within the clusters. Efficient capture of CTC clusters will enable the detailed characterization of their biological properties and role in metastasis.

  • Circulating Tumor Cell clusters are oligoclonal precursors of breast cancer metastasis
    Cell, 2014
    Co-Authors: Nicola Aceto, Maria C Donaldson, Amanda Engstrom, David T Miyamoto, Aditya Bardia, Ben S Wittner, Joel A Spencer, Adam Pely, Huili Zhu, Brian W Brannigan
    Abstract:

    Circulating Tumor Cell clusters (CTC clusters) are present in the blood of patients with cancer but their contribution to metastasis is not well defined. Using mouse models with tagged mammary Tumors, we demonstrate that CTC clusters arise from oligoclonal Tumor Cell groupings and not from intravascular aggregation events. Although rare in the circulation compared with single CTCs, CTC clusters have 23- to 50-fold increased metastatic potential. In patients with breast cancer, single-Cell resolution RNA sequencing of CTC clusters and single CTCs, matched within individual blood samples, identifies the Cell junction component plakoglobin as highly differentially expressed. In mouse models, knockdown of plakoglobin abrogates CTC cluster formation and suppresses lung metastases. In breast cancer patients, both abundance of CTC clusters and high Tumor plakoglobin levels denote adverse outcomes. Thus, CTC clusters are derived from multiCellular groupings of primary Tumor Cells held together through plakoglobin-dependent interCellular adhesion, and though rare, they greatly contribute to the metastatic spread of cancer.

Klaus Pantel - One of the best experts on this subject based on the ideXlab platform.

  • biology and clinical significance of Circulating Tumor Cell subpopulations in lung cancer
    Translational lung cancer research, 2017
    Co-Authors: Linda Oflaherty, Harriet Wikman, Klaus Pantel
    Abstract:

    By identifying and tracking genetic changes in primary Tumors and metastases, patients can be stratified for the most efficient therapeutic regimen by screening for known biomarkers. However, retrieving tissues biopsies is not always feasible due to Tumor location or risk to patient. Therefore, a liquid biopsies approach offers an appealing solution to an otherwise invasive procedure. The rapid growth of the liquid biopsy field has been aided by improvements in the sensitivity and specificity of enrichment assays for isolating Circulating Tumor Cells (CTCs) from normal surrounding blood Cells. Furthermore, the identification and molecular characterization of CTCs has been shown in numerous studies to be of diagnostic and prognostic relevance in breast, prostate and colon cancer patients. Despite these advancements, and the highly metastatic nature of lung cancer, it remains a challenge to detect CTCs in advanced non-small Cell lung cancer (NSCLC). It may be that loss of epithelial features, in favor of a mesenchymal phenotype, and the highly heterogeneous nature of NSCLC CTCs contribute to their evasion from current detection methods. By identifying a broader spectrum of biomarkers that could better differentiate the various NSCLC CTCs subpopulations, it may be possible to not only improve detection rates but also to shed light on which CTC clones are likely to drive metastatic initiation. Here we review the biology of CTCs and describe a number of proteins and genetic targets which could potentially be utilized for the dissemination of heterogenic subpopulations of CTCs in NSCLC.

  • Abstract ED06-03: Circulating Tumor Cells versus Circulating Tumor Cell products
    Biomarkers and Early Detection Research, 2013
    Co-Authors: Klaus Pantel
    Abstract:

    Metastasis is the main cause of cancer-related death and prevention of metastatic relapse is, therefore, the most important goal of cancer therapy. Distant metastases harbour unique genomic characteristics not detectable in the corresponding primary Tumor of the same patient and metastases located at different sites show a considerable intra-patient heterogeneity. Thus, the mere analysis of the resected primary Tumor alone (current standard practise in oncology) or, if possible, even re-evaluation of Tumor characteristics based on the biopsy of the most accessible metastasis may not reveal sufficient information for treatment decisions. This dilemma can be solved by a new diagnostic concept: Liquid biopsy, i.e., analysis of therapeutic targets and drug resistance-conferring gene mutations on Circulating Tumor Cells (CTCs) and Cell-free Circulating Tumor DNA (ctDNA) released into the peripheral blood from metastatic deposits. In addition, Cell-free microRNAs in the peripheral blood of cancer patients may provide real-time insights into the biology of cancer, including the effects of therapeutic interventions. MicroRNA levels in plasma, serum, urine and other body fluids have been used to detect cancer, predict the prognosis and response to therapy. Here the current challenges and future perspectives of CTCs and Circulating nucleic acids as biomarkers in clinical oncology will be discussed. Both CTCs and Circulating nucleic acids are interesting complementary technologies that can be used in parallel in future trials assessing new drugs or drug combinations. We postulate that the liquid biopsy concept will contribute to a better understanding and prevention of metastatic relapse and progression in cancer patients. Citation Format: Klaus Pantel. Circulating Tumor Cells versus Circulating Tumor Cell products. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr ED06-03.

  • Circulating Tumor Cell isolation and diagnostics toward routine clinical use
    Cancer Research, 2011
    Co-Authors: Anja Van De Stolpe, Klaus Pantel, Stefan Sleijfer, Leon W M M Terstappen, Jaap Den M J Toonder
    Abstract:

    From February 7–11, 2011, the multidisciplinary Lorentz WorkshopCirculating Tumor Cell (CTC) Isolation and Diagnostics: Toward Routine Clinical Use was held in Leiden (The Netherlands) to discuss progress and define challenges and potential solutions for development of clinically useful Circulating Tumor Cell (CTC) diagnostics. CTCs, captured as "liquid biopsy" from blood, for counting and characterization using pathology and molecular assays, are expected to replace metastatic tissue biopsies to be used to predict drug response and resistance and to monitor therapy response and cancer recurrence. CTCs are highly heterogeneous; therefore, cancer type– specific isolation technologies, as well as complex clinical interpretation software, are required. Cancer Res; 71(18); 1–6. � 2011 AACR.

  • Pathology: Are Circulating Tumor Cells predictive of overall survival?
    Nature reviews. Clinical oncology, 2009
    Co-Authors: Klaus Pantel, Sabine Riethdorf
    Abstract:

    Comparison of Circulating Tumor Cell numbers before and after treatment is predictive for overall survival in patients with metastatic castration-resistant prostate cancer; this comparison is more helpful than prostate-specific antigen detection, according to a recent study.

Jean-yves Pierga - One of the best experts on this subject based on the ideXlab platform.

  • pathological response and Circulating Tumor Cell count identifies treated her2 inflammatory breast cancer patients with exCellent prognosis beverly 2 survival data
    Clinical Cancer Research, 2015
    Co-Authors: Helen Roche, Christelle Levy, Fleur Lerebours, J Gligorov, Jean-marc Ferrero, Mario Campone, Thierry Petit, Jean-yves Pierga, Thomas Bachelot
    Abstract:

    Purpose: The BEVERLY-2 single-arm phase II trial assessed the efficacy and safety of combining neoadjuvant chemotherapy with bevacizumab and trastuzumab for the treatment of HER2-positive inflammatory breast cancer (IBC). Here, we report the results of a preplanned survival analysis at 3 years of follow-up, along with the association between outcome and Circulating biomarkers and pathologic complete response (pCR). Experimental Design: Patients received fluorouracil, epirubicin, cyclophosphamide, and bevacizumab (cycles 1–4) and docetaxel, trastuzumab, and bevacizumab (cycles 5–8) before surgery, followed by trastuzumab and bevacizumab for 30 weeks after surgery. Circulating Tumor Cell (CTC) and endothelial Cell (CEC) counts were assessed at baseline, cycle 5, preoperative, postoperative, and at 1 year. Results: Fifty-two patients were included. The 3-year disease-free survival (DFS) rate was 68% and overall survival (OS) rate was 90%. pCR (centrally reviewed) was strongly associated with 3-year DFS [80% and 53% in patients with/without pCR, respectively ( P = 0.03)]. CTC detection also independently predicted 3-year DFS [81% vs. 43% for patients with P = 0.01)]. Patients with no CTCs detected at baseline and with pCR had a high 3-year DFS (95%). CEC changes during treatment had no prognostic value. Conclusions: Our study suggests that the prognosis of IBC relies on more than the achievement of pCR and highlights the role of early hematogenous Tumor dissemination as assessed by CTCs. Combining these two prognostic factors isolates a subgroup of IBC with exCellent survival when treated with bevacizumab- and trastuzumab-containing regimens. Clin Cancer Res; 21(6); 1298–304. ©2014 AACR .

  • single Circulating Tumor Cell detection and overall survival in nonmetastatic breast cancer
    Annals of Oncology, 2010
    Co-Authors: Francoisclement Bidard, Jean-yves Pierga, Claire Mathiot, E Brain, Suzette Delaloge, Sylvie Giachetti, M Marty, P De Cremoux
    Abstract:

    Abstract Background Circulation of cancer Cells in the blood is a mandatory step for metastasis, but Circulating Tumor Cells (CTC) have a low metastatic efficiency in preclinical animal models. In this prospective study, we reported the clinical outcome of nonmetastatic breast cancer patients according to CTC detection. Patients and methods In 115 nonmetastatic patients diagnosed with large operable or locally advanced breast cancer, we prospectively detected CTC using the CellSearch system before and after neoadjuvant chemotherapy in a phase II trial (REMAGUS02). Results At baseline, 23% of patients were CTC positive, but only 10% had >1 CTC/7.5 ml of blood. After a median follow-up of 36 months, CTC detection before chemotherapy was an independent prognostic factor for both distant metastasis-free survival [DMFS; P = 0.01, relative risk (RR) = 5.0, 95% confidence interval (CI) 1.4–17] and overall survival (OS; P = 0.007, RR = 9, 95% CI 1.8–45). CTC detection after chemotherapy was of less significance (P = 0.07 and 0.09, respectively). Moreover, CTC detection showed interesting characteristics as an individual predictive test for metastatic relapses (sensibility 55%, specificity 81%, and global accuracy 77%). Conclusions Detection of ≥1 CTC/7.5 ml before neoadjuvant chemotherapy can accurately predict OS. Our findings may change the clinical management of nonmetastatic breast cancer and indicate that the metastatic efficiency of CTC could be higher than previously reported.

  • Circulating Tumor Cell detection predicts early metastatic relapse after neoadjuvant chemotherapy in large operable and locally advanced breast cancer in a phase ii randomized trial
    Clinical Cancer Research, 2008
    Co-Authors: Jean-yves Pierga, Francoisclement Bidard, Claire Mathiot, E Brain, Suzette Delaloge, Sylvie Giachetti, Patricia De Cremoux, R J Salmon, Anne Vincentsalomon, M Marty
    Abstract:

    Purpose: Circulating Tumor Cells in blood from metastatic breast cancer patients have been reported as a surrogate marker for Tumor response and shorter survival. The aim of this study was to determine whether Circulating Tumor Cells are present in the blood of patients with large operable or locally advanced breast cancer before neoadjuvant chemotherapy and after neoadjuvant chemotherapy before surgery. Experimental Design: Blood samples of 7.5 mL were obtained on CellSave tubes from patients included in a phase II trial (REMAGUS 02). Circulating Tumor Cells were immunomagnetically separated and fluorescently stained by the CellSearch system. Blood from 20 metastatic breast cancer patients was used as a positive control. Results: From October 2004 to July 2006, preneoadjuvant chemotherapy and/or postneoadjuvant chemotherapy blood samples were obtained from 118 patients. At least 1 Circulating Tumor Cell was detected in 22 of 97 patients with preneoadjuvant chemotherapy samples (23%; 95% confidence interval, 15-31%; median, 2 Cells; range, 1-17 Cells). Circulating Tumor Cell positivity rates were 17% in 86 postneoadjuvant chemotherapy samples and 27% in all 118 patients. Persistence of Circulating Tumor Cells at the end of neoadjuvant chemotherapy was not correlated with treatment response. After a short median follow-up of 18 months, the presence of Circulating Tumor Cells ( P = 0.017), hormone receptor negativity, and large Tumor size were independent prognostic factors for shorter distant metastasis–free survival. Conclusion: Circulating Tumor Cells can be detected by the CellSearch system at a low cutoff of 1 Cell in 27% of patients receiving neoadjuvant chemotherapy. Circulating Tumor Cell detection was not correlated to the primary Tumor response but is an independent prognostic factor for early relapse.