Mp65-20 Bladder Cancer Patient-Derived Organoids: A New Frontier for Personalized Therapy

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III (MP65)1 May 2024MP65-20 BLADDER CANCER PATIENT-DERIVED ORGANOIDS: A NEW FRONTIER FOR PERSONALIZED THERAPY Riccardo Mastroianni, Carlotta Frascolla, Sara Donzelli, Claudio Pulito, Andrea Russo, Sabrina Strano, Manuela Costantini, Giovanni Blandino, and Giuseppe Simone Riccardo MastroianniRiccardo Mastroianni , Carlotta FrascollaCarlotta Frascolla , Sara DonzelliSara Donzelli , Claudio PulitoClaudio Pulito , Andrea RussoAndrea Russo , Sabrina StranoSabrina Strano , Manuela CostantiniManuela Costantini , Giovanni BlandinoGiovanni Blandino , and Giuseppe SimoneGiuseppe Simone View All Author Informationhttps://doi.org/10.1097/01.JU.0001008756.24343.22.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patient-Derived Organoids (PDOs) are proving to be reliable preclinical models for characterization of bladder cancer (BCa). PDOs can be used for molecular assessment of BCa heterogeneity, prediction of chemotherapy response and for generation of patients' biobank. This study aimed to investigate the optimal culturing conditions for BCa PDOs generation and to preliminarily evaluate PDOs response to chemotherapy treatments. METHODS: BCa tissue samples (≥3 cm3) were collected from either TURB or Radical Cystectomy (RC). For RC specimens, tissues from both peripheric tumor (PT) and central tumor (CT) were collected in order to replicate BCa heterogeneity. BCa specimens were mechanically and enzymatically digested to obtain single cells suspension and then freshly or frozen processed. Subsequently, cells were included in drops of extracellular matrix (EM) or without extracellular matrix in Ultra Low Attachment (ULA) cell culture plates and then cultured with 3 different groups of growth factors. BCa PDOs were treated with different concentrations and combinations of cisplatin (CDDP), gemcitabine (GEM) or CDDP and GEM. PDOs drugs' response was assessed by ATPlite assays upon 96 hrs of treatment. Chi-Square test was used to compare categorical variables. RESULTS: Out of 47 BCa tissues analyzed, 39 (83%) were collected from RC (Figure 1). Overall, 20 (43%) BCa PDOs were successfully generated. PDOs seeded in EM had a significantly lower success rate compared to PDOs cultured in ULA plates (EM: 19% vs ULA: 71%; p<0.001). No differences were reported in PDOs generation from fresh or frozen cells suspension (Fresh: 37% vs Freezing: 46%; p=0.51) and from peripheric or central tumor tissues (PT: 33% vs CT: 47%; p=0.38). Growth factors group 3 significantly increased PDOs generation (67%; p=0.02) (Figure 2-3). ATPlite assays reported a PDOs viability rate of 50% and 25%, with 5 µM and 10 µM CDDP, respectively, and a viability rate of 4% and 10% with 5 µM and 10 µM GEM. The combination of CDDP and GEM did not have a synergic effect, mainly due to the strong cytotoxic effect of GEM. CONCLUSIONS: We successfully developed successful culture conditions for BCa PDOs generation. By closely replicating the complexity of BCa tissue, PDOs seem to provide a promising tool to preclinically evaluate response to chemotherapy treatments, paving the way for the modern precision medicine. Download PPTDownload PPTDownload PPTDownload PPT Source of Funding: No © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1084 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Riccardo Mastroianni More articles by this author Carlotta Frascolla More articles by this author Sara Donzelli More articles by this author Claudio Pulito More articles by this author Andrea Russo More articles by this author Sabrina Strano More articles by this author Manuela Costantini More articles by this author Giovanni Blandino More articles by this author Giuseppe Simone More articles by this author Expand All Advertisement PDF downloadLoading ...