Targeting EZH2 with tazemetostat
Mené en France sur 43 patients atteints d'une tumeur solide de stade avancé et sur 21 patients atteints d'un lymphome non hodgkinien réfractaire ou récidivant, cet essai de phase I évalue l'activité antitumorale, les caractéristiques pharmacocinétiques et pharmacodynamiques, la dose maximale tolérée et la toxicité du tazémétostat, un inhibiteur sélectif d'EZH2
Enhancer of zeste homolog 2 (EZH2) is a subunit of the chromatin remodelling polycomb repressive complex 2. EZH2 is a histone methyltransferase and trimethylates histone H3 lysine 27 (H3K27). EZH2 activation contributes to epigenetic transcriptional silencing because H3K27 methylation is a repressive histone modification.1 Physiologically, EZH2 activity is high in stem or progenitor cells, in which EZH2 represses genes associated with cell cycle arrest and promotes self-renewal. However, in differentiated cells EZH2 activity is opposed by the switch/sucrose non-fermentable (SWI/SNF) multiprotein complex, which promotes terminal differentiation and regulates self-renewal.
The Lancet Oncology , commentaire, 2017