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Les multiples emplois ďimatinib dans les tumeurs solides

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Les thérapies ciblées

Part of the book series: Oncologie pratique ((ONCOLPRAT))

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Abstrait

Ľimatinib mésylate (STI-571) est un inhibiteur sélectif des tyrosines kinases KIT, Platelet-Derived Growth Factor Receptors (PDGFRs), BCR-ABL, ABL, c-FMS et ARG (1). Ľimatinib est une petite molécule orale qui agit par inhibition compétitive avec le site de fixation de ľATP dans la kinase, inhibant de ce fait ľactivité de la kinase et bloquant ľactivation des voies de la transduction du signal impliquées notamment dans la prolifération cellulaire et ľapoptose (2). Synthétisé en 1993, ľimatinib a ďabord été développé dans la leucémie myéloïde chronique (LMC), caractérisée par une translocation spécifique dont le gène de fusion BCR-ABL produit une protéine à activité tyrosine kinase responsable de cette leucémie. Ľefficacité remarquable de ľimatinib dans toutes les phases de la LMC, constituant une véritable révolution dans le traitement de cette maladie, a rapidement fait envisager son utilisation dans ďautres tumeurs présentant une protéine à activité tyrosine-kinase anormalement exprimée. Cependant, les tyrosines kinases cibles ďimatinib peuvent être présentes dans les cellules tumorales dans deux situations différentes. Lorsque ľanomalie moléculaire causale intervient précocement ou de façon causale dans le processus ďoncogenèse (BCR-ABL pour les LMC par exemple), ľimatinib semble actif pour le traitement de ces affections où la kinase activée est au centre du processus de transformation. En revanche, ľefficacité ďimatinib est plus hypothétique si les kinases sont exprimées plus tardivement dans le processus de transformation (KIT dans les cancers du poumon à petites cellules par exemple).

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  1. Service ďoncologie médicale, CHU de la Timone, 13335, Marseille Cedex 5

    F. Duffaud

  2. Service ďoncologie médicale, Institut Gustave-Roussy, 39, rue Camille-Desmoulins, 94800, Villejuif

    A. Le Cesne

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Duffaud, F., Le Cesne, A. (2008). Les multiples emplois ďimatinib dans les tumeurs solides. In: Les thérapies ciblées. Oncologie pratique. Springer, Paris. https://doi.org/10.1007/978-2-287-36008-4_7

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  • DOI: https://doi.org/10.1007/978-2-287-36008-4_7

  • Publisher Name: Springer, Paris

  • Print ISBN: 978-2-287-36007-7

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