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Title: Patient-derived pancreatic tumour organoids identify therapeutic responses to oncolytic adenoviruses.
Author: 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
Keywords: Càncer de pàncrees
Teràpia genètica
Pancreas cancer
Gene therapy
Issue Date: 25-May-2020
Publisher: Elsevier
Abstract: 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.
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It is part of: EBioMedicine, 2020, vol. 56, num. 102786
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ISSN: 2352-3964
Appears in Collections:Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)

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