EZH2 inhibition for epithelioid sarcoma and follicular lymphoma
Menés respectivement sur 99 patients atteints d'un lymphome folliculaire récidivant ou réfractaire (durée médiane de suivi : 22 mois) et sur 62 patients atteints d'un sarcome épithélioïde de stade avancé caractérisé par la perte de fonction de INI1/SMARCB1 (durée médiane de suivi : 13,8 mois), ces deux essais de phase II évaluent l'efficacité, du point de vue du taux de réponse objective, et la toxicité du tazémétostat, un inhibiteur de EZH2 dispensé par voie orale
Genome-driven precision oncology culminating from the human genome project, the availabilityof clinical next-generation sequencing, and the development of kinase inhibitors hastransformed our understanding of the landscape of cancers driven by multiple oncogenes(eg, KIT, BRAF, EGFR, and RET). Yet, comprehensive genomic profiling has still not impacted the standard-of-caretherapies for most types of sarcomas and lymphomas. There are more than 100 different sarcoma subtypes, which have traditionally beengrouped together for clinical trials in a one-size-fits-all approach, and oncogene-drivenclinical next-generation sequencing is not mainstream for the treatment of lymphomas.In The Lancet Oncology, Mrinal Gounder and colleagues and Franck Morschhauser and colleagues show that an epigenetic-directed therapy, which inhibits the EZH2 methyltransferase,shows activity in patients with sarcoma and lymphoma subtypes that have been inherentlydifficult to treat, and have shown that this therapy can be clinically efficacious.
The Lancet Oncology , commentaire, 2019