Mostrar el registro sencillo del ítem

dc.contributor.author
Fraunhoffer Navarro, Nicolas Alejandro  
dc.contributor.author
Moreno Vega, Aura I.  
dc.contributor.author
Meilerman Abuelafia, Miriam Analia  
dc.contributor.author
Morvan, Marie  
dc.contributor.author
Lebarbier, Emilie  
dc.contributor.author
Mary Huard, Tristan  
dc.contributor.author
Zimmermann, Michael T.  
dc.contributor.author
Lomberk, Gwen  
dc.contributor.author
Urrutia, Raul  
dc.contributor.author
Dusetti, Nelson  
dc.contributor.author
Blum, Yuna  
dc.contributor.author
Nicolle, Rémy  
dc.contributor.author
Iovanna, Juan  
dc.date.available
2024-12-09T09:24:25Z  
dc.date.issued
2023-05  
dc.identifier.citation
Fraunhoffer Navarro, Nicolas Alejandro; Moreno Vega, Aura I.; Meilerman Abuelafia, Miriam Analia; Morvan, Marie; Lebarbier, Emilie; et al.; Priming therapy by targeting enhancer-initiated pathways in patient-derived pancreatic cancer cells; Elsevier; eBioMedicine; 92; 5-2023; 1-15  
dc.identifier.issn
2352-3964  
dc.identifier.uri
http://hdl.handle.net/11336/249731  
dc.description.abstract
Background: Systems biology leveraging multi-OMICs technologies, is rapidly advancing development of precision therapies and matching patients to targeted therapies, leading to improved responses. A new pillar of precision oncology lies in the power of chemogenomics to discover drugs that sensitizes malignant cells to other therapies. Here, we test a chemogenomic approach using epigenomic inhibitors (epidrugs) to reset patterns of gene expression driving the malignant behavior of pancreatic tumors. Methods: We tested a targeted library of ten epidrugs targeting regulators of enhancers and super-enhancers on reprogramming gene expression networks in seventeen patient-derived primary pancreatic cancer cell cultures (PDPCCs), of both basal and classical subtypes. We subsequently evaluated the ability of these epidrugs to sensitize pancreatic cancer cells to five chemotherapeutic drugs that are clinically used for this malignancy. Findings: To comprehend the impact of epidrug priming at the molecular level, we evaluated the effect of each epidrugs at the transcriptomic level of PDPCCs. The activating epidrugs showed a higher number of upregulated genes than the repressive epidrugs (χ2 test p-value <0.01). Furthermore, we developed a classifier using the baseline transcriptome of epidrug-primed-chemosensitized PDPCCs to predict the best epidrug-priming regime to a given chemotherapy. Six signatures with a significant association with the chemosensitization centroid (R ≤ −0.80; p-value < 0.01) were identified and validated in a subset of PDPCCs. Interpretation: We conclude that targeting enhancer-initiated pathways in patient-derived primary cells, represents a promising approach for developing new therapies for human pancreatic cancer.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Elsevier  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/  
dc.subject
PDAC  
dc.subject
EPIDRUGS  
dc.subject
CHEMOTHERAPY  
dc.subject
PRIMING  
dc.subject.classification
Otras Medicina Básica  
dc.subject.classification
Medicina Básica  
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Priming therapy by targeting enhancer-initiated pathways in patient-derived pancreatic cancer cells  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2024-11-25T15:21:25Z  
dc.journal.volume
92  
dc.journal.pagination
1-15  
dc.journal.pais
Reino Unido  
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: Moreno Vega, Aura I.. No especifíca;  
dc.description.fil
Fil: Meilerman Abuelafia, Miriam Analia. Inserm; Francia  
dc.description.fil
Fil: Morvan, Marie. Universite Paris Ouest Nanterre la Defense; Francia  
dc.description.fil
Fil: Lebarbier, Emilie. Inserm; Francia  
dc.description.fil
Fil: Mary Huard, Tristan. Universite Paris-Saclay ;  
dc.description.fil
Fil: Zimmermann, Michael T.. Medical College Of Wisconsin; Estados Unidos  
dc.description.fil
Fil: Lomberk, Gwen. Medical College Of Wisconsin; Estados Unidos  
dc.description.fil
Fil: Urrutia, Raul. Medical College Of Wisconsin; Estados Unidos  
dc.description.fil
Fil: Dusetti, Nelson. Inserm; Francia  
dc.description.fil
Fil: Blum, Yuna. Inserm; Francia  
dc.description.fil
Fil: Nicolle, Rémy. Inserm; Francia  
dc.description.fil
Fil: Iovanna, Juan. Inserm; Francia  
dc.journal.title
eBioMedicine  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.ebiom.2023.104602  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2352396423001676