MP07-18 PERSISTENCE OF CIRCULATING TUMOUR CELLS (CTCS) IN MEN TREATED WITH ANDROGEN DEPRIVATION THERAPY CAN BE USED TO ENRICH AND PROPAGATE TEMPORARY PERSONALIZED CELL LINES

Abstract

You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 2016MP07-18 PERSISTENCE OF CIRCULATING TUMOUR CELLS (CTCS) IN MEN TREATED WITH ANDROGEN DEPRIVATION THERAPY CAN BE USED TO ENRICH AND PROPAGATE TEMPORARY PERSONALIZED CELL LINES Handoo Rhee, Jennifer Gunter, Lidja Jovanovic, Elizabeth Williams, Brett Hollier, Colleen Nelson, and Ian Vela Handoo RheeHandoo Rhee More articles by this author , Jennifer GunterJennifer Gunter More articles by this author , Lidja JovanovicLidja Jovanovic More articles by this author , Elizabeth WilliamsElizabeth Williams More articles by this author , Brett HollierBrett Hollier More articles by this author , Colleen NelsonColleen Nelson More articles by this author , and Ian VelaIan Vela More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2221AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen deprivation therapy (ADT) plays a pivotal role in managing men with metastatic prostate cancer. Whilst it provides cancer specific survival advantage in those with metastatic disease and those undergoing radiotherapy for intermediate to high risk localized prostate cancer, it is associated with significant metabolic adverse effects. ADMET (ADT and metformin) trial was set up to determine whether adjuvant metformin would reverse metabolic syndrome induced by ADT, and whether molecular changes in CTCs could be detected during the treatment. METHODS We established a multi-centre randomized, placebo controlled clinical trial. In total, 80 patients with metastatic prostate cancer who are commenced on ADT are expected to be recruited and reviewed 6 weekly for 42 weeks. Forty seven patients have so far been screened as a part of the trial. 5ml of whole blood was collected from patients for CTC enrichment, enumeration and propagation. Enrichment was performed using CD45 negative selection kit (RosetteSep). CTCs were identified using immunofluorescence imaging with antibodies against prostate specific antigen, cytokeratin, CD45 and nucleus. Cells were propagated in customized stem cell solution with hypoxic conditions (8%). RESULTS At screening, 39 of 47 patients demonstrated circulating tumour cells with the mean number of 847 (range 1-4750, SD+/-1731). In 32 of 39 samples, the enriched samples could be propagated temporarily with the peak population being reached at 7-20 days. Cells were cultured in both 2D and 3D conditions and temporary organoids could be developed from 12 patients. Cultured cells were then prepared for RNA extraction, with the ultimate aim of being able to propagate enough samples for RNA sequencing. With the ability to further culture the harvested CTCs, we were able to observe the cells under the influence of numerous prostate cancer treatment medications using Incucyte, demonstrating the potential for personalized medicine. In 26 patients, who were available for longitudinal follow up, all patients demonstrated persistence of CTCs. CONCLUSIONS Circulating tumour cell technology remains a viable option as a means of providing biomarker information and tumour activity indicator in delivering precision medicine. Firstly, enumeration can be used to help determine the response to a treatment. Secondly, temporary culture and progression into development of organoids may be used to allow for downstream analysis and therapeutic decision. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e83-e84 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Handoo Rhee More articles by this author Jennifer Gunter More articles by this author Lidja Jovanovic More articles by this author Elizabeth Williams More articles by this author Brett Hollier More articles by this author Colleen Nelson More articles by this author Ian Vela More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...