Circumventing glioblastoma resistance to temozolomide through optimal drug combinations designed by systems pharmacology and machine learning.

Journal: British journal of pharmacology
Published Date: Apr 14, 2025

Abstract

BACKGROUND AND PURPOSE: Glioblastoma (GBM), the most frequent and aggressive brain tumour in adults, is associated with a dismal prognostic despite intensive treatment involving surgery, radiotherapy and temozolomide (TMZ)-based chemotherapy. The initial or acquired resistance of GBM to TMZ appeals for precision medicine approaches to the design of novel efficient combination pharmacotherapies. Such investigation needs to account for the overexpression of the O6-methylguanine-DNA methyl-transferase (MGMT) repair enzyme which is responsible for TMZ resistance in patients.

Authors

  • Sergio Corridore
    INSERM Unit 1331, Institut Curie, PSL Research University, CBIO-Center for Computational Biology, Mines Paris, Cancer Systems Pharmacology team, Saint Cloud, France.
  • Maïté Verreault
    AP-HP, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, DMU Neurosciences, Service de Neuro-Oncologie-Institut de Neurologie, Sorbonne Université, Paris, France.
  • Hugo Martin
    INSERM Unit 1331, Institut Curie, PSL Research University, CBIO-Center for Computational Biology, Mines Paris, Cancer Systems Pharmacology team, Saint Cloud, France.
  • Thibault Delobel
    INSERM Unit 1331, Institut Curie, PSL Research University, CBIO-Center for Computational Biology, Mines Paris, Cancer Systems Pharmacology team, Saint Cloud, France.
  • Cécile Carrère
    Institut Denis Poisson, Université d'Orléans, CNRS, Orléans, France.
  • Ahmed Idbaih
    Sorbonne Université, INSERM U1127, CNRS UMR7225, Institut du Cerveau et de la Moelle épinière (ICM), AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France shair@hadassah.org.il ahmed.idbaih@aphp.fr.
  • Annabelle Ballesta
    INSERM Unit 1331, Institut Curie, PSL Research University, CBIO-Center for Computational Biology, Mines Paris, Cancer Systems Pharmacology team, Saint Cloud, France.

Keywords

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