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https://www.readbyqxmd.com/read/29319382/ctc-derived-ar-v7-detection-as-a-prognostic-and-predictive-biomarker-in-advanced-prostate-cancer
#1
Diogo A Bastos, Emmanuel S Antonarakis
Prostate cancer is a highly heterogeneous disease, with remarkably different prognosis across all stages. Increased circulating tumor cell (CTC) count (≥ 5) using the CellSearch assay has been identified as one of the markers that can be used to predict survival, with added value beyond currently available prognostic factors. Recently, androgen receptor splice variant 7 (AR-V7) detection has been associated with worse outcomes for patients with castration-resistant prostate cancer (CRPC) treated with novel androgen receptor-signaling (ARS) inhibitors such as abiraterone and enzalutamide but not taxane chemotherapies...
January 10, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29301749/in-situ-detection-and-quantification-of-ar-v7-ar-fl-psa-and-kras-point-mutations-in-circulating-tumor-cells
#2
Amin El-Heliebi, Claudia Hille, Navya Laxman, Jessica Svedlund, Christoph Haudum, Erkan Ercan, Thomas Kroneis, Shukun Chen, Maria Smolle, Christopher Rossmann, Tomasz Krzywkowski, Annika Ahlford, Evangelia Darai, Gunhild von Amsberg, Winfried Alsdorf, Frank König, Matthias Löhr, Inge de Kruijff, Sabine Riethdorf, Tobias M Gorges, Klaus Pantel, Thomas Bauernhofer, Mats Nilsson, Peter Sedlmayr
BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs...
January 4, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29301747/an-rna-based-digital-circulating-tumor-cell-signature-is-predictive-of-drug-response-and-early-dissemination-in-prostate-cancer
#3
David T Miyamoto, Richard J Lee, Mark Kalinich, Joseph LiCausi, Yu Zheng, Tianqi Chen, John D Milner, Erin Emmons, Uyen Ho, Katherine Broderick, Erin Silva, Sarah Javaid, Tanya Todorova Kwan, Xin Hong, Douglas M Dahl, Francis J McGovern, Jason A Efstathiou, Matthew R Smith, Lecia V Sequist, Ravi Kapur, Chin-Lee Wu, Shannon L Stott, David T Ting, Anita Giobbie-Hurder, Mehmet Toner, Shyamala Maheswaran, Daniel A Haber
Blood-based biomarkers are critical in metastatic prostate cancer, where characteristic bone metastases are not readily sampled, and they may enable risk stratification in localized disease. We established a sensitive and high-throughput strategy for analyzing prostate circulating tumor cells (CTCs) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 metastatic castration-resistant prostate cancer patients treated with first-line abiraterone, pretreatment elevation of the digital CTCM Score identifies a high risk population with poor overall survival (HR 6...
January 4, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29289429/synaptophysin-expression-on-circulating-tumor-cells-in-patients-with-castration-resistant-prostate-cancer-undergoing-treatment-with-abiraterone-acetate-or-enzalutamide
#4
Sumanta K Pal, Miaoling He, Lin Chen, Lixin Yang, Raju Pillai, Przemyslaw Twardowski, JoAnn Hsu, Marcin Kortylewski, Jeremy O Jones
BACKGROUND: With the advent of secondary androgen receptor (AR)-targeted therapies in metastatic castration resistant prostate cancer (PC), nonadenocarcinoma PCs are becoming more prevalent. Many of these cancers express neuroendocrine markers, which may provide biomarkers for emergence of this disease state. We aimed to quantify the expression of synaptophysin (Syp) on circulating tumor cells (CTCs) from serial samples of patients being treated with abiraterone acetate or enzalutamide...
December 27, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29289318/reducing-wbc-background-in-cancer-cell-separation-products-by-negative-acoustic-contrast-particle-immuno-acoustophoresis
#5
Kevin Cushing, Eva Undvall, Yvonne Ceder, Hans Lilja, Thomas Laurell
Cancer cells display acoustic properties enabling acoustophoretic separation from white blood cells (WBCs) with 2-3 log suppression of the WBC background. However, a subset of WBCs has overlapping acoustic properties with cancer cells, which is why label-free acoustophoretic cancer cell isolation needs additional purification prior to analysis. This paper reports for the first time a proof of concept for continuous flow acoustophoretic negative selection of WBCs from cancer cells using negative acoustic contrast elastomeric particles (EPs) activated with CD45-antibodies that specifically bind to WBCs...
February 13, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29285777/analogous-detection-of-circulating-tumor-cells-using-the-accucyte%C3%A2-cytefinder%C3%A2-system-and-iset-system-in-patients-with-locally-advanced-and-metastatic-prostate-cancer
#6
Emma E van der Toom, Vincent P Groot, Stephanie A Glavaris, Georgios Gemenetzis, Heather J Chalfin, Laura D Wood, Christopher L Wolfgang, Jean J M C H de la Rosette, Theo M de Reijke, Kenneth J Pienta
INTRODUCTION: Circulating tumor cells (CTCs) can provide important information on patient's prognosis and treatment efficacy. Currently, a plethora of methods is available for the detection of these rare cells. We compared the outcomes of two of those methods to enumerate and characterize CTCs in patients with locally advanced and metastatic prostate cancer (PCa). First, the selection-free AccuCyte® - CyteFinder® system (RareCyte® , Inc., Seattle, WA) and second, the ISET system (Rarecells Diagnostics, France), a CTC detection method based on cell size-exclusion...
December 29, 2017: Prostate
https://www.readbyqxmd.com/read/29230413/establishment-and-application-of-prostate-cancer-circulating-tumor-cells-in-the-era-of-precision-medicine
#7
REVIEW
Yoon Seok Suh, Jae Young Joung, Sung Han Kim, Ho Kyung Seo, Jinsoo Chung, Kang Hyun Lee
Prostate cancer (PC) is the second most common cancer in men and is the fifth leading cause of cancer-related deaths worldwide. Additionally, there is concern for overdiagnosis and overtreatment of PC. Thus, selection of an appropriate candidate for active surveillance as well as more accurate and less invasive tools for monitoring advanced PC is required. Circulating tumor cells (CTCs) have emerged as a liquid biopsy tool; there have been several reports on its role, technologies, and applications to various cancers, including PC...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29170762/clinical-utility-of-clia-grade-ar-v7-testing-in-patients-with-metastatic-castration-resistant-prostate-cancer
#8
Mark C Markowski, John L Silberstein, James R Eshleman, Mario A Eisenberger, Jun Luo, Emmanuel S Antonarakis
Purpose: A splice variant of the androgen receptor, AR-V7, confers resistance to AR-targeted therapies (ATTs) but not taxane chemotherapies in patients with metastatic castration-resistant prostate cancer. Since August 2015, a clinical-grade assay to detect AR-V7 messenger RNA expression in circulating tumors cells (CTCs) has been available to providers through a Clinical Laboratory Improvement Amendments-certified laboratory at Johns Hopkins University. Methods: We contacted ordering providers of the first 150 consecutive tests by using a questionnaire-based survey to determine how the results of AR-V7 testing were used to influence clinical practice...
2017: JCO Precision Oncology
https://www.readbyqxmd.com/read/29170510/whole-blood-stabilization-for-the-microfluidic-isolation-and-molecular-characterization-of-circulating-tumor-cells
#9
Keith H K Wong, Shannon N Tessier, David T Miyamoto, Kathleen L Miller, Lauren D Bookstaver, Thomas R Carey, Cleo J Stannard, Vishal Thapar, Eric C Tai, Kevin D Vo, Erin S Emmons, Haley M Pleskow, Rebecca D Sandlin, Lecia V Sequist, David T Ting, Daniel A Haber, Shyamala Maheswaran, Shannon L Stott, Mehmet Toner
Precise rare-cell technologies require the blood to be processed immediately or be stabilized with fixatives. Such restrictions limit the translation of circulating tumor cell (CTC)-based liquid biopsy assays that provide accurate molecular data in guiding clinical decisions. Here we describe a method to preserve whole blood in its minimally altered state by combining hypothermic preservation with targeted strategies that counter cooling-induced platelet activation. Using this method, whole blood preserved for up to 72 h can be readily processed for microfluidic sorting without compromising CTC yield and viability...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158826/label-free-biochips-for-accurate-detection-of-prostate-cancer-in-the-clinic-dual-biomarkers-and-circulating-tumor-cells
#10
Lung-Hsuan Pan, See-Tong Pang, Po-Yu Fang, Cheng-Keng Chuang, Hung-Wei Yang
Purpose: Early diagnosis of prostate cancer (PCa) is essential for the prevention of metastasis and for early treatment; therefore, we aimed to develop a simple, accurate, and multi-analyte assay system for early PCa diagnosis in this study. Experimental design: We fabricated three kinds of biochips then integrated into microfluidic device for simultaneous detection of vascularendothelial growth factor (VEGF), prostate-specific antigen (PSA), and PCa circulating tumor cells (CTC) in human serum for accurate diagnosis of PCa...
2017: Theranostics
https://www.readbyqxmd.com/read/29122836/multiplex-gene-expression-profiling-of-in-vivo-isolated-circulating-tumor-cells-in-high-risk-prostate-cancer-patients
#11
Athina Markou, Marifili Lazaridou, Panagiotis Paraskevopoulos, Shukun Chen, Monika Świerczewska, Joanna Budna, Andra Kuske, Tobias M Gorges, Simon A Joosse, Thomas Kroneis, Maciej Zabel, Peter Sedlmayr, Catherine Alix-Panabières, Klaus Pantel, Evi S Lianidou
BACKGROUND: Molecular characterization of circulating tumor cells (CTCs) is important for selecting patients for targeted treatments. We present, for the first time, results on gene expression profiling of CTCs isolated in vivo from high-risk prostate cancer (PCa) patients compared with CTC detected by 3 protein-based assays-CellSearch®, PSA-EPISPOT, and immunofluorescence of CellCollector® in vivo-captured CTCs-using the same blood draw. METHODS: EpCAM-positive CTCs were isolated in vivo using the CellCollector from 108 high-risk PCa patients and 36 healthy volunteers...
November 9, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29105802/circulating-micrornas-and-treatment-response-in-the-phase-ii-swog-s0925-study-for-patients-with-new-metastatic-hormone-sensitive-prostate-cancer
#12
Heather H Cheng, Melissa Plets, Hongli Li, Celestia S Higano, Catherine M Tangen, Neeraj Agarwal, Nicholas J Vogelzang, Maha Hussain, Ian M Thompson, Muneesh Tewari, Evan Y Yu
BACKGROUND: Previous studies suggest circulating, blood-based microRNAs (miRNAs) may serve as minimally invasive prostate cancer biomarkers, however there is limited data from prospective clinical trials. Here, we explore the role of candidate plasma miRNAs as potential biomarkers in the SWOG 0925 randomized phase II study of androgen deprivation combined with cixutumumab versus androgen deprivation alone in patients with new metastatic hormone-sensitive prostate cancer. METHODS: Correlative biospecimens, including circulating tumor cells (CTCs) and plasma for miRNA analysis, were collected at baseline and after 12 weeks on treatment from 50 patients enrolled on SWOG 0925...
November 6, 2017: Prostate
https://www.readbyqxmd.com/read/29102858/weekly-cabazitaxel-plus-prednisone-is-effective-and-less-toxic-for-unfit-metastatic-castration-resistant-prostate-cancer-phase-ii-spanish-oncology-genitourinary-group-sogug-trial
#13
Miguel Ángel Climent, Begoña Pérez-Valderrama, Begoña Mellado, Eva María Fernández Parra, Ovidio Fernández Calvo, María Ochoa de Olza, Laura Muinelo Romay, Urbano Anido, Montserrat Domenech, Susana Hernando Polo, José Ángel Arranz Arija, Cristina Caballero, María José Juan Fita, Daniel Castellano
AIM: Cabazitaxel (CBZ), a novel tubulin-binding taxane, improves overall survival in metastatic castration-resistant prostate cancer (mCRPC) that progresses during or after docetaxel treatment. We have designed a phase II study to evaluate the efficacy and safety of CBZ as a weekly schedule for 'unfit' mCRPC patients after docetaxel failure. METHODS: In this single arm phase II study. CBZ was weekly administered in 1-hour infusion on days 1, 8, 15 and 22, every 5 weeks at 10 mg/m(2) to eligible 'unfit' patients; oral prednisone (5 mg) was administered twice a day...
November 2, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29071394/-study-on-the-prediction-of-ar-v7-and-ctc-circulation-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc-correlation-between-common-clinical-outcome-parameters-rpfs-os-ctc-changes-and-ar-v7-status-androgen-receptor-splice-variant-7-in-patients
#14
https://www.readbyqxmd.com/read/29069718/androgen-receptor-amplification-is-concordant-between-circulating-tumor-cells-and-biopsies-from-men-undergoing-treatment-for-metastatic-castration-resistant-prostate-cancer
#15
Jennifer Podolak, Kristi Eilers, Timothy Newby, Rachel Slottke, Erin Tucker, Susan B Olson, Hui-Wen Lue, Jack Youngren, Rahul Aggarwal, Eric J Small, Julie N Graff, Joshi J Alumkal, Tomasz M Beer, George V Thomas
Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH)...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29059273/a-randomized-double-blind-placebo-controlled-phase-ii-study-of-maintenance-therapy-with-tasquinimod-in-patients-with-metastatic-castration-resistant-prostate-cancer-responsive-to-or-stabilized-during-first-line-docetaxel-chemotherapy
#16
K Fizazi, A Ulys, L Sengeløv, M Moe, S Ladoire, A Thiery-Vuillemin, A Flechon, A Guida, J Bellmunt, M A Climent, S Chowdhury, H Dumez, M Matouskova, N Penel, S Liutkauskiene, L Stachurski, C N Sternberg, F Baton, N Germann, G Daugaard
Background: This phase II study was conducted to assess clinical efficacy of tasquinimod maintenance therapy in patients with metastatic castrate-resistant prostate cancer not progressing during first-line docetaxel-based therapy. Patients and methods: Patients were randomly assigned (1 : 1) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire and analgesic use...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29050295/a-comprehensive-study-of-circulating-tumour-cells-at-the-moment-of-prostate-cancer-diagnosis-biological-and-clinical-implications-of-egfr-ar-and-snps
#17
Ignacio Puche-Sanz, María J Alvarez-Cubero, Manrique Pascual-Geler, Alba Rodríguez-Martínez, Miguel Delgado-Rodríguez, José L García-Puche, José Expósito, Inmaculada Robles-Fernández, Carmen Entrala-Bernal, José A Lorente, José M Cózar-Olmo, María J Serrano
Circulating tumor cells (CTCs) have been recently accepted as prognostic markers in metastatic prostate cancer (PCa). However, very few studies have analyzed their role in early-stage PCa. The aim of this research is to study the value of CTCs at the moment of PCa diagnosis and to identify different subpopulations of CTCs. Patients with PSA value > 4 ng/ml and clinical suspicion of PCa were included. Samples were collected immediately before prostatic biopsy. CTCs were isolated by immunomagnetic technique using a multi-CK specific antibody...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904887/biology-and-clinical-significance-of-circulating-tumor-cell-subpopulations-in-lung-cancer
#18
REVIEW
Linda O'Flaherty, Harriet Wikman, Klaus Pantel
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...
August 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28903443/radioligand-therapy-of-metastatic-prostate-cancer-using-177-lu-psma-617-after-radiation-exposure-to-223-ra-dichloride
#19
Hojjat Ahmadzadehfar, Stefanie Zimbelmann, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Florian C Gaertner, Xiao Wei, Stefan Hauser, Markus Essler
Radioligand therapy with (177)Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with (223)Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of (177)Lu-PSMA-617 after exposure to more cycles of (223)Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with (223)Ra...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903376/improving-circulating-tumor-cells-enumeration-and-characterization-to-predict-outcome-in-first-line-chemotherapy-mcrpc-patients
#20
Luis León-Mateos, Helena Casas, Alicia Abalo, María Vieito, Manuel Abreu, Urbano Anido, Antonio Gómez-Tato, Rafael López, Miguel Abal, Laura Muinelo-Romay
INTRODUCTION: There is a critical need of new surrogate markers for improving the therapeutic selection and monitoring of metastatic prostate cancer patients. Nowadays clinical management of these patients is been driven by biochemical and clinical parameters without enough accuracy to allow a real personalized medicine. The present study was conducted to go insight the molecular profile of circulating tumor cells (CTCs) isolated from advanced metastatic castration-resistant prostate cancer (mCRPC) with the aim of identifying prognostic marker with potential utility for therapy selection and monitoring...
August 15, 2017: Oncotarget
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