PD47-12 CHACTERISATION OF BLADDER CANCER DRUG RESPONSES IN ORGANOIDS AND EX VIVO MODELS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV (PD47)1 Apr 2020PD47-12 CHACTERISATION OF BLADDER CANCER DRUG RESPONSES IN ORGANOIDS AND EX VIVO MODELS Mirjam Kiener, Sofia Karkampouna, Federico La Manna, Marta De Menna, George N. Thalmann*, Roland Seiler-Blarer, and Marianna Kruithof-de Julio Mirjam KienerMirjam Kiener More articles by this author , Sofia KarkampounaSofia Karkampouna More articles by this author , Federico La MannaFederico La Manna More articles by this author , Marta De MennaMarta De Menna More articles by this author , George N. Thalmann*George N. Thalmann* More articles by this author , Roland Seiler-BlarerRoland Seiler-Blarer More articles by this author , and Marianna Kruithof-de JulioMarianna Kruithof-de Julio More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000934.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder cancer (BLCa) is the tenth most common cancer worldwide with more than 500’000 newly diagnosed cases each year. Non-muscle invasive BLCa (NMIBC) and muscle invasive BLCa (MIBC) have specific clinical profiles and require different treatment approaches. However, they underrepresent the clinical complexity of patients. Thus, characterisation of BLCa subtypes is crucial to account for tumor heterogeneity. Effectiveness of cisplatin therapy was linked to four molecular subtypes of MIBC. Pre-clinical models, such as patient-derived organoids (PDOs) and ex vivo tissue culture, are useful tools to screen drugs and tailor medical care to a patient’s individual genetic background. Here we aim to characterise drug responses of BLCa samples and correlate to molecular subtypes based on transcriptomic profiles. Moreover, we explore the applicability of our pre-clinical models to determine drug sensitivity profiles of BLCa patients and personalize chemotherapy accordingly. METHODS: Human NMIBC and MIBC samples were treated in ex vivo tissue culture with cisplatin and gemcitabine. Drug response and tumor subtype were studied by immunohistochemistry and RNA sequencing. PDOs were cultured in suspension in defined medium. PDO composition and molecular subtype was characterised by immunofluorescence staining. The drug responsiveness of PDOs was evaluated by CellTiter Glo 3D viability assay. RESULTS: The phenotype of parental tumor was maintained ex vivo. Basal subtypes responded most favourably to cisplatin and cisplatin/gemcitabine combination treatment, whereas a luminal NMIBC sample was insensitive to cisplatin. Heterogeneity of PDOs from MIBC and NMIBC samples was maintained in culture and reflected the molecular subtype of the parental tissue. Drug sensitivity of PDOs to conventional chemotherapy and a panel of >10 FDA-approved experimental compounds was assessed within 2-3 weeks from surgery. Drug screens on organoids derived from different patients revealed distinct drug responses. Moreover, sensitivity to Cisplatin/Gemcitabine combination treatment in PDOs reflected therapy response in the patient. CONCLUSIONS: Patient-derived BLCa responds differentially to drug treatments. Future studies will show if our pre-clinical findings correlate to clinical and molecular parameters to improve patient stratification and treatment regimens. Source of Funding: Swiss National Science Foundation (SNF) © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e929-e930 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mirjam Kiener More articles by this author Sofia Karkampouna More articles by this author Federico La Manna More articles by this author Marta De Menna More articles by this author George N. Thalmann* More articles by this author Roland Seiler-Blarer More articles by this author Marianna Kruithof-de Julio More articles by this author Expand All Advertisement PDF downloadLoading ...