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mCRPC Blood biomarkers

Claire Fletcher
PURPOSE OF REVIEW: Recent clinical introduction of the novel antiandrogen, Enzalutamide (Enza), CYP17 inhibitor, Abiraterone (Abi), and the second-generation chemotherapeutic, Cabazitaxel, has increased survival of patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). However, de novo and acquired resistance rates are high. A liquid biopsy that can rapidly, sensitively and robustly identify which patients will respond to treatment in a minimally invasive manner is urgently required to permit switch to a potentially more efficacious drug regimen, thus increasing survival whilst avoiding debilitating side effects associated with unnecessary treatment...
September 2017: Current Opinion in Urology
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...
May 19, 2017: Oncotarget
Howard I Scher, Ryon P Graf, Nicole A Schreiber, Brigit McLaughlin, David Lu, Jessica Louw, Daniel C Danila, Lyndsey Dugan, Ann Johnson, Glenn Heller, Martin Fleisher, Ryan Dittamore
BACKGROUND: Circulating tumor cells (CTCs) expressing AR-V7 protein localized to the nucleus (nuclear-specific) identify metastatic castration-resistant prostate cancer (mCRPC) patients with improved overall survival (OS) on taxane therapy relative to the androgen receptor signaling inhibitors (ARSi) abiraterone acetate, enzalutamide, and apalutamide. OBJECTIVE: To evaluate if expanding the positivity criteria to include both nuclear and cytoplasmic AR-V7 localization ("nuclear-agnostic") identifies more patients who would benefit from a taxane over an ARSi...
June 2017: European Urology
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
Santosh Gupta, Jing Li, Gabor Kemeny, Rhonda L Bitting, Joshua Beaver, Jason A Somarelli, Kathryn E Ware, Simon Gregory, Andrew J Armstrong
PURPOSE: Beyond enumeration, circulating tumor cells (CTCs) can provide genetic information from metastatic cancer that may facilitate a greater understanding of tumor biology and enable a precision medicine approach. EXPERIMENTAL DESIGN: CTCs and paired leukocytes from men with metastatic castration-resistant prostate cancer (mCRPC) were isolated from blood through red cell lysis, CD45 depletion, and flow sorting based on EpCAM/CD45 expression. We next performed whole genomic copy number analysis of CTCs and matched patient leukocytes (germline) using array-based comparative genomic hybridization (aCGH) from 16 men with mCRPC, including longitudinal and sequential aCGH analyses of CTCs in the context of enzalutamide therapy...
September 6, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Tilman Todenhöfer, Arun Azad, Craig Stewart, Jian Gao, Bernhard J Eigl, Martin E Gleave, Anthony M Joshua, Peter C Black, Kim N Chi
PURPOSE: The expression of AR-V7 (androgen receptor splice variant) 7 in circulating tumor cells has been associated with resistance to abiraterone and enzalutamide in patients with metastatic castration resistant prostate cancer. We used a sensitive, whole blood reverse transcriptase-polymerase chain reaction assay that does not require circulating tumor cell enrichment to correlate outcomes of abiraterone with whole blood expression of AR-V7 and other prostate cancer associated transcripts...
January 2017: Journal of Urology
Howard I Scher, David Lu, Nicole A Schreiber, Jessica Louw, Ryon P Graf, Hebert A Vargas, Ann Johnson, Adam Jendrisak, Richard Bambury, Daniel Danila, Brigit McLaughlin, Justin Wahl, Stephanie B Greene, Glenn Heller, Dena Marrinucci, Martin Fleisher, Ryan Dittamore
Importance: A critical decision in the management of metastatic castration-resistant prostate cancer (mCRPC) is when to administer an androgen receptor signaling (ARS) inhibitor or a taxane. Objective: To determine if pretherapy nuclear androgen-receptor splice variant 7 (AR-V7) protein expression and localization on circulating tumor cells (CTCs) is a treatment-specific marker for response and outcomes between ARS inhibitors and taxanes. Design, Setting, and Participants: For this cross-sectional cohort study at Memorial Sloan Kettering Cancer Center, 265 men with progressive mCRPC undergoing a change in treatment were considered; 86 were excluded because they were not initiating ARS or taxane therapy; and 18 were excluded for processing time constraints, leaving 161 patients for analysis...
November 1, 2016: JAMA Oncology
Won Jin Cho, Daniel S M Oliveira, Abdo J Najy, Leandro E Mainetti, Hussein D Aoun, Michael L Cher, Elisabeth Heath, Hyeong-Reh C Kim, R Daniel Bonfil
BACKGROUND: Characterization of genes linked to bone metastasis is critical for identification of novel prognostic or predictive biomarkers and potential therapeutic targets in metastatic castrate-resistant prostate cancer (mCRPC). Although bone marrow core biopsies (BMBx) can be obtained for gene profiling, the procedure itself is invasive and uncommon practice in mCRPC patients. Conversely, circulating tumor cells (CTCs), which are likely to stem from bone metastases, can be isolated from blood...
March 15, 2016: Journal of Translational Medicine
Aseem Anand, Michael J Morris, Steven M Larson, David Minarik, Andreas Josefsson, John T Helgstrand, Peter S Oturai, Lars Edenbrandt, Martin Andreas Røder, Anders Bjartell
BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the automated BSI in predicting overall survival (OS) in mCRPC patients being treated with enzalutamide. METHODS: Retrospectively, we included patients who received enzalutamide as a clinically approved therapy for mCRPC and had undergone bone scan prior to starting therapy...
December 2016: EJNMMI Research
Òscar Reig, Mercedes Marín-Aguilera, Gemma Carrera, Natalia Jiménez, Laia Paré, Susana García-Recio, Lydia Gaba, Maria Verónica Pereira, Pedro Fernández, Aleix Prat, Begoña Mellado
TMPRSS2-ERG rearrangement is a genetic alteration exclusive to prostate cancer, associated with taxane resistance in preclinical models. Its detection in blood samples of metastatic resistant prostate cancer (mCRPC) patients may indicate the presence of circulating tumour cells with this genetic alteration and may predict taxane resistance. To test this hypothesis, we evaluated TMPRSS2-ERG expression using quantitative reverse transcription polymerase chain reaction in peripheral blood mononuclear cells and tumour tissue from mCPRC patients treated with taxanes...
November 2016: European Urology
Kun Chang, Yun-Yi Kong, Bo Dai, Ding-Wei Ye, Yuan-Yuan Qu, Yue Wang, Zhong-Wei Jia, Gao-Xiang Li
Although circulating tumor cell (CTC) enumeration in peripheral blood has already been validated as a reliable biomarker in predicting prognosis in metastatic castration-resistant prostate cancer (mCRPC), patients with favorable CTC counts (CTC < 5/7.5 ml) still experience various survival times. Assays that can reduce patients' risks are urgently needed. In this study, we set up a real-time quantitative polymerase chain reaction (RT-qPCR) method to detect epithelial-mesenchymal transition (EMT) and stem cell gene expression status in peripheral blood to validate whether they could complement CTC enumeration...
December 8, 2015: Oncotarget
Edwin E Reyes, David J VanderWeele, Masis Isikbay, Ryan Duggan, Alexa Campanile, Walter M Stadler, Donald J Vander Griend, Russell Z Szmulewitz
BACKGROUND: Many current therapies for metastatic castration-resistant prostate cancer (mCRPC) are aimed at AR signaling; however, resistance to these therapies is inevitable. To personalize CRPC therapy in an individual with clinical progression despite maximal AR signaling blockade, it is important to characterize the status of AR activity within their cancer. Biopsies of bone metastases are invasive and frequently fail to yield sufficient tissue for further study. Evaluation of circulating tumor cells (CTCs) offers an alternative, minimally invasive mechanism to characterize and study late-stage disease...
November 26, 2014: Journal of Translational Medicine
Takatsugu Okegawa, Naoshi Itaya, Hidehiko Hara, Mitsuhiro Tambo, Kikuo Nutahara
AIM: We examined whether Circulating Tumor Cells (CTCs) can be used to predict survival in patients with bone-metastatic castration-resistant-prostate cancer (mCRPC) treated with docetaxel chemotherapy. PATIENTS AND METHODS: All patients with mCRPC who had experienced treatment failure with androgen deprivation therapy and had received docetaxel chemotherapy were eligible for study inclusion. CTCs in whole blood were enumerated with the CellSearch System. RESULTS: The median CTC count at baseline before starting trial treatment was 7 (range=0-227) CTCs per 7...
November 2014: Anticancer Research
Amir Goldkorn, Benjamin Ely, Catherine M Tangen, Yu-Chong Tai, Tong Xu, Hongli Li, Przemyslaw Twardowski, Peter J Van Veldhuizen, Neeraj Agarwal, Michael A Carducci, J Paul Monk, Mark Garzotto, Philip C Mack, Primo Lara, Celestia S Higano, Maha Hussain, Nicholas J Vogelzang, Ian M Thompson, Richard J Cote, David I Quinn
Circulating tumor cells (CTC) are promising biomarkers in metastatic castration resistant prostate cancer (mCRPC), and telomerase activity (TA) is a recognized cancer marker. Therefore, we hypothesized that CTC TA may be prognostic of overall survival (OS) in mCRPC. To test this, we used a novel Parylene-C slot microfilter to measure live CTC TA in S0421, a phase III SWOG-led therapeutic trial. Blood samples underwent CTC capture and TA measurement by microfilter, as well as parallel enumeration by CellSearch (Janssen/J&J)...
April 15, 2015: International Journal of Cancer. Journal International du Cancer
Douglas G McNeel, Thomas A Gardner, Celestia S Higano, Philip W Kantoff, Eric J Small, Mark H Wener, Robert B Sims, Todd DeVries, Nadeem A Sheikh, Robert Dreicer
Sipuleucel-T is an autologous cellular immunotherapy used to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Traditional short-term indicators of clinical response commonly used with chemotherapy have not correlated with survival in patients treated with sipuleucel-T. This retrospective study aimed to evaluate laboratory parameters as possible early biomarkers associated with clinical benefit following sipuleucel-T treatment. Patients treated with sipuleucel-T from three randomized, controlled, phase III clinical trials in mCRPC were considered: IMPACT (NCT00065442; n = 512), D9901 (NCT00005947; n = 127), and D9902A (NCT01133704; n = 98)...
October 2014: Cancer Immunology Research
Pawel Osmulski, Devalingam Mahalingam, Maria E Gaczynska, Joseph Liu, Susan Huang, Aaron M Horning, Chiou-Miin Wang, Ian M Thompson, Tim H-M Huang, Chun-Liang Chen
BACKGROUND: Emerging evidence shows that nanomechanical phenotypes of circulating tumor cells (CTC) could become potential biomarkers for metastatic castration resistant prostate cancer (mCRPC). METHODS: To determine the nanomechanical phenotypes of CTCs we applied atomic force microscopy (AFM) employing the PeakForce quantitative nanomechanical (QNM) imaging. We assessed biophysical parameters (elasticity, deformation, and adhesion) of 130 CTCs isolated from blood samples from five castration sensitive (CS) and 12 castration resistant prostate cancer (CRPCa) patients...
September 2014: Prostate
Daniel C Danila, Aseem Anand, Nikolaus Schultz, Glenn Heller, Mingliang Wan, Clifford C Sung, Charles Dai, Raya Khanin, Martin Fleisher, Hans Lilja, Howard I Scher
BACKGROUND: Biomarkers based on detecting prostate cancer (PCa)-specific transcripts in blood are associated with inferior outcomes, but their validation in a clinical context is lacking. OBJECTIVE: To determine whether detecting enhanced transcripts for PCa in whole blood using an analytically valid assay has prognostic significance relative to circulating tumor cell (CTC) enumeration. DESIGN, SETTING, AND PARTICIPANTS: The detection of KLK3, KLK2, HOXB13, GRHL2, and FOXA1 in whole blood by reverse transcription polymerase chain reaction (RT-PCR) was studied in 97 men with metastatic castration-resistant PCa (mCRPC) as a prognostic factor for overall survival...
June 2014: European Urology
Luke A Selth, Scott Townley, Joanna L Gillis, Aleksandra M Ochnik, Krisna Murti, Robyn J Macfarlane, Kim N Chi, Villis R Marshall, Wayne D Tilley, Lisa M Butler
Circulating microRNAs (miRNAs) are emerging as useful non-invasive markers of disease. The objective of this study was to use a mouse model of prostate cancer as a tool to discover serum miRNAs that could be assessed in a clinical setting. Global miRNA profiling identified 46 miRNAs at significantly altered levels (p ≤ 0.05) in the serum of TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice with advanced prostate cancer compared to healthy controls. A subset of these miRNAs with known human homologues were validated in an independent cohort of mice and then measured in serum from men with metastatic castration-resistant prostate cancer (mCRPC; n = 25) or healthy men (n = 25)...
August 1, 2012: International Journal of Cancer. Journal International du Cancer
Oscar B Goodman, James T Symanowski, Aida Loudyi, Louis M Fink, David C Ward, Nicholas J Vogelzang
UNLABELLED: Little information exists regarding the utility circulating tumor cell (CTC) enumeration in hormone sensitive prostate cancer. We enumerated CTC in 33 consecutive patients undergoing androgren deprivation therapy (ADT) at our institution. Multivariate analysis revealed baseline CTC as the only independent predictor of progression to CRPC. These data suggest that baseline CTC may identify those unlikely to benefit from ADT. INTRODUCTION: Circulating tumor cell (CTC) enumeration by using the Cellsearch platform has established prognostic and predictive value in patients with metastatic castration-resistant prostate cancer (mCRPC)...
September 2011: Clinical Genitourinary Cancer
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