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dc.contributor.author
Hoare, Owen
dc.contributor.author
Fraunhoffer Navarro, Nicolas Alejandro
dc.contributor.author
Elkaoutari, Abdessamad
dc.contributor.author
Gayet, Odile
dc.contributor.author
Bigonnet, Martin
dc.contributor.author
Roques, Julie
dc.contributor.author
Nicolle, Rémy
dc.contributor.author
McGuckin, Colin
dc.contributor.author
Forraz, Nico
dc.contributor.author
Sohier, Emilie
dc.contributor.author
Tonon, Laurie
dc.contributor.author
Wajda, Pauline
dc.contributor.author
Boyault, Sandrine
dc.contributor.author
Attignon, Valéry
dc.contributor.author
Tabone, Luciana Belen
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Barbier, Sandrine
dc.contributor.author
Mignard, Caroline
dc.contributor.author
Duchamp, Olivier
dc.contributor.author
Iovanna, Juan
dc.contributor.author
Dusetti, Nelson J.
dc.date.available
2022-12-22T09:58:25Z
dc.date.issued
2021-05
dc.identifier.citation
Hoare, Owen; Fraunhoffer Navarro, Nicolas Alejandro; Elkaoutari, Abdessamad; Gayet, Odile; Bigonnet, Martin; et al.; Exploring the complementarity of pancreatic ductal adenocarcinoma preclinical models; MDPI; Cancers; 13; 10; 5-2021; 1-13
dc.identifier.issn
2072-6694
dc.identifier.uri
http://hdl.handle.net/11336/182099
dc.description.abstract
Purpose: Compare pancreatic ductal adenocarcinoma (PDAC), preclinical models, by their transcriptome and drug response landscapes to evaluate their complementarity. Experimental De-sign: Three paired PDAC preclinical models—patient‐derived xenografts (PDX), xenograft‐derived pancreatic organoids (XDPO) and xenograft‐derived primary cell cultures (XDPCC)—were derived from 20 patients and analyzed at the transcriptomic and chemosensitivity level. Transcriptomic characterization was performed using the basal‐like/classical subtyping and the PDAC molecular gradient (PAMG). Chemosensitivity for gemcitabine, irinotecan, 5‐fluorouracil and oxaliplatin was established and the associated biological pathways were determined using independent component analysis (ICA) on the transcriptome of each model. The selection criteria used to identify the different components was the chemosensitivity score (CSS) found for each drug in each model. Results: PDX was the most dispersed model whereas XDPO and XDPCC were mainly classical and basal-like, respectively. Chemosensitivity scoring determines that PDX and XDPO display a positive correlation for three out of four drugs tested, whereas PDX and XDPCC did not correlate. No match was observed for each tumor chemosensitivity in the different models. Finally, pathway analysis shows a significant association between PDX and XDPO for the chemosensitivity‐associated pathways and PDX and XDPCC for the chemoresistance‐associated pathways. Conclusions: Each PDAC preclinical model possesses a unique basal‐like/classical transcriptomic phenotype that strongly in-fluences their global chemosensitivity. Each preclinical model is imperfect but complementary, sug-gesting that a more representative approach of the clinical reality could be obtained by combining them. Translational Relevance: The identification of molecular signatures that underpin drug sensitivity to chemotherapy in PDAC remains clinically challenging. Importantly, the vast majority of studies using preclinical in vivo and in vitro models fail when transferred to patients in a clinical setting despite initially promising results. This study presents for the first time a comparison between three preclinical models directly derived from the same patients. We show that their applica-bility to preclinical studies should be considered with a complementary focus, avoiding tumor-based direct extrapolations, which might generate misleading conclusions and consequently the overlook of clinically relevant features.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
MDPI
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
CHEMOSENSITIVITY PREDICTION
dc.subject
IN VITRO MODELS
dc.subject
IN VIVO MODELS
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PANCREATIC CANCER
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PERSONALIZED MEDICINE
dc.subject.classification
Patología
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Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Exploring the complementarity of pancreatic ductal adenocarcinoma preclinical models
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-09-21T14:13:20Z
dc.journal.volume
13
dc.journal.number
10
dc.journal.pagination
1-13
dc.journal.pais
Países Bajos
dc.description.fil
Fil: Hoare, Owen. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Fraunhoffer Navarro, Nicolas Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
dc.description.fil
Fil: Elkaoutari, Abdessamad. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Gayet, Odile. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Bigonnet, Martin. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Roques, Julie. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Nicolle, Rémy. No especifíca;
dc.description.fil
Fil: McGuckin, Colin. Cell Therapy Research Institute; Francia
dc.description.fil
Fil: Forraz, Nico. Cell Therapy Research Institute; Francia
dc.description.fil
Fil: Sohier, Emilie. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; Francia
dc.description.fil
Fil: Tonon, Laurie. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; Francia
dc.description.fil
Fil: Wajda, Pauline. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; Francia
dc.description.fil
Fil: Boyault, Sandrine. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; Francia
dc.description.fil
Fil: Attignon, Valéry. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; Francia
dc.description.fil
Fil: Tabone, Luciana Belen. Le Centre Régional de Lutte Contre Le Cancer Léon Bérard; Francia
dc.description.fil
Fil: Barbier, Sandrine. No especifíca;
dc.description.fil
Fil: Mignard, Caroline. No especifíca;
dc.description.fil
Fil: Duchamp, Olivier. No especifíca;
dc.description.fil
Fil: Iovanna, Juan. Centre National de la Recherche Scientifique; Francia
dc.description.fil
Fil: Dusetti, Nelson J.. Centre National de la Recherche Scientifique; Francia
dc.journal.title
Cancers
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3390/cancers13102473
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