Fillat i Fonts, CristinaRaimondi, GiuliaUniversitat de Barcelona. Facultat de Farmàcia i Ciències de l'Alimentació2021-03-242021-06-082020-06-08https://hdl.handle.net/2445/175693[eng] The general goal of this thesis has been to progress oncolytic adenovirus therapy for PDAC, by the incorporation of novel preclinical models to test for patient-specific responses and the generation of oncolytic adenoviruses with enhanced therapeutic index. The two main objectives have been the following: i) Evaluate patients-derived organoids (PDOs) technology as a platform to screen for personalized virotherapy in vitro 1) Establishment of a battery of PDOs from PDAC and normal pancreatic tissues, and evaluation of their applicability in the study of adenoviral infection; 2) Screening of a battery of PDOs to identify individual sensitivities to virotherapies, and the effects derived from the combination with chemotherapy; 3) Study virotherapy-responses in metastasis originated from PDOs xenografted in mice; (ii) Improve oncolytic adenovirus potency by modulation of miRNAs deregulated in PDAC 4) Screening of aberrantly expressed miRNAs sensitizing viral oncolysis in PDAC via CRISPR/Cas9 system; 5) Generation of a miRNA sponge-adenovirus and evaluation of its oncolytic effects in vitro and in vivo; 6) Modulation of miRNA levels with the THZ1 transcriptional inhibitor, and assessment of the effects of its combination with oncolytic adenoviruses.271 p.application/pdfengcc by (c) Raimondi, Giulia, 2021http://creativecommons.org/licenses/by/3.0/es/OncologiaAdenovirusMicro RNAsCultius cel·lulars humansOncologyAdenovirusesMicroRNAsHuman cell cultureinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccesshttp://hdl.handle.net/10803/671205