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https://www.readbyqxmd.com/read/28228136/circulating-tumor-cells-capture-disease-evolution-in-advanced-prostate-cancer
#1
Justin Lack, Marc Gillard, Maggie Cam, Gladell P Paner, David J VanderWeele
BACKGROUND: Genetic analysis of advanced cancer is limited by availability of representative tissue. Biopsies of prostate cancer metastasized to bone are invasive with low quantity of tumor tissue. The prostate cancer genome is dynamic, however, with temporal heterogeneity requiring repeated evaluation as the disease evolves. Circulating tumor cells (CTCs) offer an alternative, "liquid biopsy", though single CTC sequencing efforts are laborious with high failure rates. METHODS: We performed exome sequencing of matched treatment-naïve tumor tissue, castrate resistant tumor tissue, and pooled CTC samples, and compared mutations identified in each...
February 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28202223/filtration-based-enrichment-of-circulating-tumor-cells-from-all-prostate-cancer-risk-groups
#2
Julius Adebayo Awe, Jeff Saranchuk, Darrel Drachenberg, Sabine Mai
OBJECTIVE: To combine circulating tumor cell (CTC) isolation by filtration and immunohistochemistry to investigate the presence of CTCs in low, intermediate, and high-risk prostate cancer (PCa). CTCs isolated from these risk groups stained positive for both cytokeratin and androgen receptors, but negative for CD45. PATIENTS AND METHODS: Blood samples from 41 biopsy confirmed patients with PCa at different clinical stages such as low, intermediate, and high risk were analyzed...
February 12, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28181495/expression-of-%C3%AE-globin-by-cancer-cells-promotes-cell-survival-during-blood-borne-dissemination
#3
Yu Zheng, David T Miyamoto, Ben S Wittner, James P Sullivan, Nicola Aceto, Nicole Vincent Jordan, Min Yu, Nezihi Murat Karabacak, Valentine Comaills, Robert Morris, Rushil Desai, Niyati Desai, Erin Emmons, John D Milner, Richard J Lee, Chin-Lee Wu, Lecia V Sequist, Wilhelm Haas, David T Ting, Mehmet Toner, Sridhar Ramaswamy, Shyamala Maheswaran, Daniel A Haber
Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction of β-globin (HBB), but not its partner α-globin (HBA). The tumour-specific origin of HBB is confirmed by sequence polymorphisms within human xenograft-derived CTCs in mouse models. Increased intracellular reactive oxygen species (ROS) in cultured breast CTCs triggers HBB induction, mediated through the transcriptional regulator KLF4...
February 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28178640/a-phase-i-ii-study-of-the-investigational-drug-alisertib-in-combination-with-abiraterone-and-prednisone-for-patients-with-metastatic-castration-resistant-prostate-cancer-progressing-on-abiraterone
#4
Jianqing Lin, Sheel A Patel, Ashwin R Sama, Jean H Hoffman-Censits, Brooke Kennedy, Deborah Kilpatrick, Zhong Ye, Hushan Yang, Zhaomei Mu, Benjamin Leiby, Nancy Lewis, Massimo Cristofanilli, William Kevin Kelly
LESSONS LEARNED: Patients with metastatic castration-resistant prostate cancer did not tolerate the combination of alisertib with abiraterone and prednisone.There was no clear signal indicating that adding alisertib might be beneficial for those patients progressing on abiraterone. BACKGROUND: We hypothesized that Aurora A kinase (AK) contributes to castrate resistance in prostate cancer (PCa) and that inhibiting AK with alisertib can resensitize PCa cells to androgen receptor (AR) inhibitor abiraterone...
November 2016: Oncologist
https://www.readbyqxmd.com/read/28153390/nucleolin-staining-may-aid-in-the-identification-of-circulating-prostate-cancer-cells
#5
Heather J Chalfin, James E Verdone, Emma E van der Toom, Stephanie Glavaris, Michael A Gorin, Kenneth J Pienta
INTRODUCTION: Circulating tumor cells (CTCs) have great potential as circulating biomarkers for solid malignancies. Currently available assays for CTC detection rely on epithelial markers with somewhat limited sensitivity and specificity. We found that the staining pattern of nucleolin, a common nucleolar protein in proliferative cells, separates CTCs from white blood cells (WBCs) in men with metastatic prostate cancer. PATIENTS AND METHODS: Whole peripheral blood from 3 men with metastatic prostate cancer was processed with the AccuCyte CTC system (RareCyte, Seattle, WA)...
January 4, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28152506/detection-fidelity-of-ar-mutations-in-plasma-derived-cell-free-dna
#6
Alexa Goldstein, Patricia Valda Toro, Justin Lee, John L Silberstein, Mary Nakazawa, Ian Waters, Karen Cravero, David Chu, Rory L Cochran, Minsoo Kim, Daniel Shinn, Samantha Torquato, Robert M Hughes, Aparna Pallavajjala, Michael A Carducci, Channing J Paller, Samuel R Denmeade, Bruce Kressel, Bruce J Trock, Mario A Eisenberger, Emmanuel S Antonarakis, Ben H Park, Paula J Hurley
Somatic genetic alterations including copy number and point mutations in the androgen receptor (AR) are associated with resistance to therapies targeting the androgen/AR axis in patients with metastatic castration resistant prostate cancer (mCRPC). Due to limitations associated with biopsying metastatic lesions, plasma derived cell-free DNA (cfDNA) is increasingly being used as substrate for genetic testing. AR mutations detected by deep next generation sequencing (NGS) of cfDNA from patients with mCRPC have been reported at allelic fractions ranging from over 25% to below 1%...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28009470/proportion-of-circulating-tumor-cell-clusters-increases-during-cancer-metastasis
#7
Yuanzhen Suo, Chengying Xie, Xi Zhu, Zhichao Fan, Zhangru Yang, Hao He, Xunbin Wei
Circulating tumor cell (CTC) clusters are found among CTCs and show significantly greater potential for an important role in cancer metastasis than single CTCs, which have been traditionally believed as the majority of CTCs. The accurate proportion and dynamics of CTC clusters remain unclear due to the fact that CTCs in blood flow are very difficult to detect in vivo and in vitro. CTC clusters are even more difficult to be distinguished from CTCs without perturbation by state-of-the-art detection methods. Here, we demonstrate that by using in vivo flow cytometry (IVFC), we can reliably measure the proportion and dynamics of CTC clusters in two murine tumor models...
December 23, 2016: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28000772/improved-detection-of-circulating-tumor-cells-in-non-metastatic-high-risk-prostate-cancer-patients
#8
Andra Kuske, Tobias M Gorges, Pierre Tennstedt, Anne-Kathrin Tiebel, Raisa Pompe, Felix Preißer, Sandra Prues, Martine Mazel, Athina Markou, Evi Lianidou, Sven Peine, Catherine Alix-Panabières, Sabine Riethdorf, Burkhard Beyer, Thorsten Schlomm, Klaus Pantel
The relevance of blood-based assays to monitor minimal residual disease (MRD) in non-metastatic prostate cancer (PCa) remains unclear. Proving that clinically relevant circulating tumor cells (CTCs) can be detected with available technologies could address this. This study aimed to improve CTC detection in non-metastatic PCa patients by combining three independent CTC assays: the CellSearch system, an in vivo CellCollector and the EPISPOT. Peripheral blood samples from high-risk PCa patients were screened for CTCs before and three months after radical prostatectomy (RP)...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27956006/dynamics-of-three-dimensional-telomere-profiles-of-circulating-tumor-cells-in-patients-with-high-risk-prostate-cancer-who-are-undergoing-androgen-deprivation-and-radiation-therapies
#9
Landon Wark, Thomas Klonisch, Julius Awe, Cecile LeClerc, Brandon Dyck, Harvey Quon, Sabine Mai
INTRODUCTION: Accurate assessment and monitoring of the therapeutic efficacy of locally advanced prostate cancer remains a major clinical challenge. Contrary to prostate biopsies, circulating tumor cells (CTCs) are a cellular source repeatedly obtainable by blood sampling and could serve as a surrogate marker for treatment efficacy. In this study, we used size-based filtration to isolate and enumerate CTCs from the blood of 20 patients with high-risk (any one of cT3, Gleason 8-10, or prostate-specific antigen>20ng/ml), nonmetastatic, and treatment-naive prostate cancer before and after androgen deprivation therapy (ADT) and radiation therapy (RT)...
March 2017: Urologic Oncology
https://www.readbyqxmd.com/read/27936891/comparison-of-different-contouring-definitions-of-the-rectum-as-organ-at-risk-oar-and-dose-volume-parameters-predicting-rectal-inflammation-in-radiotherapy-of-prostate-cancer-which-definition-to-use
#10
COMPARATIVE STUDY
Mirko Nitsche, Werner Brannath, Matthias Brückner, Dirk Wagner, Alexander Kaltenborn, Nils Temme, Robert M Hermann
OBJECTIVE: The objective of this retrospective planning study was to find a contouring definition for the rectum as an organ at risk (OAR) in curative three-dimensional external beam radiotherapy (EBRT) for prostate cancer (PCa) with a predictive correlation between the dose-volume histogram (DVH) and rectal toxicity. METHODS: In a pre-study, the planning CT scans of 23 patients with PCa receiving definitive EBRT were analyzed. The rectum was contoured according to 13 different definitions, and the dose distribution was correlated with the respective rectal volumes by generating DVH curves...
February 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/27928807/prognostic-value-of-circulating-tumor-cells-in-castration-resistant-prostate-cancer-a-meta-analysis
#11
Yuxiao Zheng, Cheng Zhang, Jie Wu, Gong Cheng, Haiwei Yang, Lixin Hua, Zengjun Wang
PURPOSE: The prognostic value of circulating tumor cells (CTC) detected in castration-resistant prostate cancer(CRPC) is currently under debate. The aim of our meta-analysis was to evaluate the prognostic effect of CTC andto elucidate whether the detection of CTC in the peripheral blood (PB) of patients diagnosed with CRPC can beused as an independent prognostic factor for survival. MATERIALS AND METHODS: The Pubmed, Science Citation Index, Cochrane Database, Embase Cell Research databaseand the references in relevant studies were systematically searched...
8, 2016: Urology Journal
https://www.readbyqxmd.com/read/27916908/epidermal-growth-factor-receptor-status-in-circulating-tumor-cells-as-a-predictive-biomarker-of-sensitivity-in-castration-resistant-prostate-cancer-patients-treated-with-docetaxel-chemotherapy
#12
Takatsugu Okegawa, Naoshi Itaya, Hidehiko Hara, Mitsuhiro Tambo, Kikuo Nutahara
OBJECTIVE: We examined whether epidermal growth factor receptor (EGFR) expression in circulating tumor cells (CTCs) can be used to predict survival in a population of bone-metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel chemotherapy. METHODS: All patients with mCRPC who had experienced treatment failure with androgen-deprivation therapy and had received docetaxel chemotherapy were eligible. CTCs and EGFR expression in CTCs were enumerated with the CellSearch System in whole blood...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27872478/circulating-tumour-cells-as-biomarkers-of-prostate-bladder-and-kidney-cancer
#13
REVIEW
Michael A Gorin, James E Verdone, Emma van der Toom, Trinity J Bivalacqua, Mohamad E Allaf, Kenneth J Pienta
Circulating tumour cells (CTCs) have been studied as biomarkers of a number of solid malignancies. Potential clinical applications for CTC analysis include early cancer detection, disease staging, monitoring for recurrence, prognostication, and to aid in the selection of therapy. In the field of urologic oncology, CTCs have been most widely studied as prognostic biomarkers of castration-resistant prostate cancer. Additionally, emerging data support a role for CTCs to help identify which patients are most likely to respond to novel androgen-pathway targeted therapies, such as abiraterone and enzalutamide...
November 22, 2016: Nature Reviews. Urology
https://www.readbyqxmd.com/read/27851748/chromosomal-instability-estimation-based-on-next-generation-sequencing-and-single-cell-genome-wide-copy-number-variation-analysis
#14
Stephanie B Greene, Angel E Dago, Laura J Leitz, Yipeng Wang, Jerry Lee, Shannon L Werner, Steven Gendreau, Premal Patel, Shidong Jia, Liangxuan Zhang, Eric K Tucker, Michael Malchiodi, Ryon P Graf, Ryan Dittamore, Dena Marrinucci, Mark Landers
Genomic instability is a hallmark of cancer often associated with poor patient outcome and resistance to targeted therapy. Assessment of genomic instability in bulk tumor or biopsy can be complicated due to sample availability, surrounding tissue contamination, or tumor heterogeneity. The Epic Sciences circulating tumor cell (CTC) platform utilizes a non-enrichment based approach for the detection and characterization of rare tumor cells in clinical blood samples. Genomic profiling of individual CTCs could provide a portrait of cancer heterogeneity, identify clonal and sub-clonal drivers, and monitor disease progression...
2016: PloS One
https://www.readbyqxmd.com/read/27843207/chemotherapy-options-in-castration-resistant-prostate-cancer
#15
REVIEW
Benjamin A Teply, Ralph J Hauke
INTRODUCTION: The treatment landscape for patients with metastatic castration-resistant prostate cancer (CRPC) is evolving, with recent approvals of immune therapy, novel hormonal therapy, and bone-targeted therapy. Chemotherapy remains an essential component of the armamentarium. Herein, we review current chemotherapy options for patients with CRPC and discuss future challenges. METHODS: We reviewed literature for chemotherapy agents in prostate cancer, with special attention to the evidence for efficacy of the currently approved agents...
October 2016: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/27793843/her2-and-egfr-overexpression-support-metastatic-progression-of-prostate-cancer-to-bone
#16
Kathleen C Day, Guadalupe Lorenzatti Hiles, Molly Kozminsky, Scott J Dawsey, Alyssa Paul, Luke J Broses, Rajal Shah, Lakshmi P Kunja, Christopher Hall, Nallasivam Palanisamy, Stephanie Daignault-Newton, Layla El-Sawy, Steven James Wilson, Andrew Chou, Kathleen Woods Ignatoski, Evan Keller, Dafydd Thomas, Sunitha Nagrath, Todd Morgan, Mark L Day
Activation of the EGF receptors EGFR (ErbB1) and HER2 (ErbB2) drives the progression of multiple cancer types through complex mechanisms that are still not fully understood. In this study, we report that HER2 expression is elevated in bone metastases of prostate cancer independently of gene amplification. An examination of HER2 and NF-κB receptor (RANK) coexpression revealed increased levels of both proteins in aggressive prostate tumors and metastatic deposits. Inhibiting HER2 expression in bone tumor xenografts reduced proliferation and RANK expression while maintaining EGFR expression...
January 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27783057/dissecting-the-heterogeneity-of-circulating-tumor-cells-in-metastatic-breast-cancer-going-far-beyond-the-needle-in-the-haystack
#17
REVIEW
Michela Bulfoni, Matteo Turetta, Fabio Del Ben, Carla Di Loreto, Antonio Paolo Beltrami, Daniela Cesselli
Although the enumeration of circulating tumor cells (CTC) defined as expressing both epithelial cell adhesion molecule and cytokeratins (EpCAM⁺/CK⁺) can predict prognosis and response to therapy in metastatic breast, colon and prostate cancer, its clinical utility (i.e., the ability to improve patient outcome by guiding therapy) has not yet been proven in clinical trials. Therefore, scientists are now focusing on the molecular characterization of CTC as a way to explore its possible use as a "surrogate" of tumor tissues to non-invasively assess the genomic landscape of the cancer and its evolution during treatment...
October 24, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27769045/inducible-expression-of-cancer-testis-antigens-in-human-prostate-cancer
#18
Erika Heninger, Timothy E G Krueger, Stephanie M Thiede, Jamie M Sperger, Brianna L Byers, Madison R Kircher, David Kosoff, Bing Yang, David F Jarrard, Douglas G McNeel, Joshua M Lang
Immune tolerance to self-antigens can limit robust anti-tumor immune responses in the use of tumor vaccines. Expression of novel tumor associated antigens can improve immune recognition and lysis of tumor cells. The cancer-testis antigen (CTA) family of proteins has been hypothesized to be an ideal class of antigens due to tumor-restricted expression, a subset of which have been found to induce antibody responses in patients with prostate disease. We demonstrate that CTA expression is highly inducible in five different Prostate Cancer (PC) cell lines using a hypomethylating agent 5-Aza-2'-deoxycytidine (5AZA) and/or a histone deacetylase inhibitor LBH589...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27764810/epithelial-to-mesenchymal-transition-leads-to-disease-stage-differences-in-circulating-tumor-cell-detection-and-metastasis-in-pre-clinical-models-of-prostate-cancer
#19
Lori E Lowes, David Goodale, Ying Xia, Carl Postenka, Matthew M Piaseczny, Freeman Paczkowski, Alison L Allan
Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of ≥5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch® system, the "gold standard" clinical platform. However, ~35% of metastatic PCa patients assessed by CellSearch® have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis...
October 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27749322/clinical-validity-of-detecting-circulating-tumor-cells-by-adnatest-assay-compared-with-direct-detection-of-tumor-mrna-in-stabilized-whole-blood-as-a-biomarker-predicting-overall-survival-for-metastatic-castration-resistant-prostate-cancer-patients
#20
Daniel C Danila, Aliaksandra Samoila, Chintan Patel, Nicole Schreiber, Amrita Herkal, Aseem Anand, Diogo Bastos, Glenn Heller, Martin Fleisher, Howard I Scher
Circulating tumor cell (CTC) number measured with the CellSearch assay is prognostic for survival in metastatic castration-resistant prostate cancer before and after therapy. Using a standard operating protocol for sample collection, processing, and analysis, we compared detection rates of CellSearch performed using US Food and Drug Administration-cleared methodology with a second positive selection assay, AdnaTest, and a nonselection polymerase chain reaction (PCR)-based (direct detection PCR [DDPCR]) assay in 55 blood samples from 47 men with progressive metastatic castration-resistant prostate cancer...
September 2016: Cancer Journal
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