| Title: |
Priming therapy by targeting enhancer-initiated pathways in patient-derived pancreatic cancer cells |
| Authors: |
Fraunhoffer, Nicolas, A; Moreno Vega, Aura I; Abuelafia, Analía Meilerman; Morvan, Marie; Lebarbier, Emilie; Mary-Huard, Tristan; Zimmermann, Michael; Lomberk, Gwen; Urrutia, Raul; Dusetti, Nelson; Blum, Yuna; Nicolle, Rémy; Iovanna, Juan |
| Contributors: |
Centre de Recherche en Cancérologie de Marseille (CRCM); Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC); Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Universidad de Buenos Aires Buenos Aires (UBA); Ligue Nationale Contre le Cancer (LNCC); Modélisation aléatoire de Paris X (MODAL'X); Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS); Mathématiques et Informatique Appliquées (MIA Paris-Saclay); AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon); AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Medical College of Wisconsin Milwaukee (MCW); Institut de Génétique et Développement de Rennes (IGDR); Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes (Biosit : Biologie - Santé - Innovation Technologique); Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); (le programme) Cartes d'identité des tumeurs (CIT); Ligue Nationales Contre le Cancer (LNCC); This work was supported by INCa (Grants number 2018-078 to ND and 2018- 079 to JI), Canceropole PACA (ND), Amidex Foundation (ND), and INSERM (JI). |
| Source: |
ISSN: 2352-3964 ; EBioMedicine ; https://hal.science/hal-04100206 ; EBioMedicine, 2023, 92, pp.104602. ⟨10.1016/j.ebiom.2023.104602⟩. |
| Publisher Information: |
HAL CCSD; Elsevier |
| Publication Year: |
2023 |
| Collection: |
Université de Rennes 1: Publications scientifiques (HAL) |
| Subject Terms: |
Epidrugs; PDAC; Priming chemotherapies; Transcriptome; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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 (χ(2) test p-value |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/37148583; PUBMED: 37148583; WOS: 000999663400001 |
| DOI: |
10.1016/j.ebiom.2023.104602 |
| Availability: |
https://hal.science/hal-04100206; https://hal.science/hal-04100206v1/document; https://hal.science/hal-04100206v1/file/2023_priming_ebiomedicine.pdf; https://doi.org/10.1016/j.ebiom.2023.104602 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.A8A3C953 |
| Database: |
BASE |