Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/178870
Patient-derived pancreatic tumour organoids identify therapeutic responses to oncolytic adenoviruses.
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Background: Pancreatic patient-derived organoids (PDOs) are a well-established model for studying pancreatic ductal adenocarcinoma (PDAC) carcinogenesis and are potential predictors of clinical responses to chemotherapy. Oncolytic virotherapy is envisioned as a novel treatment modality for pancreatic cancer, and candidate viruses are being tested in clinical trials. Here, we explore the feasibility of using PDOs as a screening platform for the oncolytic adenovirus (OA) response. Methods: Organoids were established from healthy pancreas and PDAC tissues and assessed for infectivity, oncoselectivity, and patient-dependent sensitivity to OA. Antitumour effects were studied in vivo in organoid xenografts. Further evaluation of oncolytic responses was conducted in organoids derived from orthotopic models or metastastic tissues.Findings: Oncolytic adenoviruses display good selectivity, with replication only in organoids derived from PDAC tumours. Furthermore, responses of PDOs to a set of OAs reveal individual differences in cytotoxicity as well as in synergism with standard chemotherapy. Adenoviral cytotoxicity in PDOs is predictive of antitumour efficacy in a subcutaneous xenograft setting. Organoids from orthotopic tumours and metastases in nude mice mirror the viral preference of PDOs, indicating that PDO sensitivity to OAs could be informative about responses in both primary tumours and metastatic foci. Interpretation: Our data imply that pancreatic PDOs can serve as predictive tools for screening for sensitivity to OA.
Matèries
Matèries (anglès)
Citació
Citació
RAIMONDI, Giulia, MATO BERCIANO, Ana, PASCUAL SABATER, Silvia, ROVIRA RIGAU, Maria, CUATRECASAS FREIXAS, Miriam, FONDEVILA CAMPO, Constantino, SÁNCHEZ CABÚS, Santiago, BEGTHEL, Harry, BOJ, Sylvia f., CLEVERS, Hans, FILLAT I FONTS, Cristina. Patient-derived pancreatic tumour organoids identify therapeutic responses to oncolytic adenoviruses.. _EBioMedicine_. 2020. Vol. 56, núm. 102786. [consulta: 21 de gener de 2026]. ISSN: 2352-3964. [Disponible a: https://hdl.handle.net/2445/178870]