Abstracts
Résumé
Le ciblage de l’anomalie génétique à l’origine d’une maladie constitue le nouveau défi de la recherche pharmaceutique. Précurseur en ce domaine, l’imatinib mésylate (Glivec®, Novartis) représente à l’heure actuelle une révolution dans le traitement de la leucémie myéloïde chronique, car cette molécule inhibe l’activité tyrosine kinase de l’oncogène c-abl. Bien que minoritaire, la résistance clinique au traitement de la leucémie myéloïde chronique par l’imatinib mésylate a cependant suscité bien des investigations, permettant l’acquisition de nombreuses données fondamentales concernant le mode d’action des tyrosine kinases et certains mécanismes moléculaires associés à l’évolution de la maladie. Par ailleurs, la compréhension des bases moléculaires de cette résistance a permis de montrer que la spécificité de l’imatinib mésylate présente des limites, l’utilisation prolongée de ce médicament chez des patients porteurs de certaines mutations ponctuelles de c-abl pouvant précipiter l’évolution de la maladie. Cet article expose comment l’histoire de l’utilisation de l’imatinib mésylate représente un exemple de parfaite synergie entre l’expérimentation clinique et la recherche fondamentale
Summary
For drug development and pharmaceutical research, targeting the molecular abnormalities is considered as a new challenge. A number of diseases including cancer are linked to perturbation of tyrosine kinase (TK). Imatinib (Glivec® or Gleevec®, Novartis), the most potent inhibitor of c-abl TK, was recently developed. This molecule has been approved in the treatment of chronic myeloid leukemia (CML). However, emergence of clinical resistance regarding a low rate of CML patients leads to intensive research. In the current article, we discuss the data and the mechanism of the resistance phenomenon. This review illustrates the important requirement to transfer back the information from patient to laboratory in order to improve future drug design.
Appendices
Références
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