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Dramatic In Vivo Efficacy of the EZH2-Inhibitor Tazemetostat in PBRM1-Mutated Human Chordoma Xenograft.
Passeri, Thibault; Dahmani, Ahmed; Masliah-Planchon, Julien; Naguez, Adnan; Michou, Marine; El Botty, Rania; Vacher, Sophie; Bouarich, Rachida; Nicolas, André; Polivka, Marc; Franck, Coralie; Schnitzler, Anne; Némati, Fariba; Roman-Roman, Sergio; Bourdeaut, Franck; Adle-Biassette, Homa; Mammar, Hamid; Froelich, Sébastien; Bièche, Ivan; Decaudin, Didier.
Afiliación
  • Passeri T; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Dahmani A; Department of Genetics, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Masliah-Planchon J; Department of Neurosurgery, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, University of Paris, 75010 Paris, France.
  • Naguez A; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Michou M; Department of Genetics, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • El Botty R; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Vacher S; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Bouarich R; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Nicolas A; Department of Genetics, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Polivka M; Integrated Cancer Research Site, Institut Curie, 75005 Paris, France.
  • Franck C; Department of Tumor Biology, Institut Curie, 75005 Paris, France.
  • Schnitzler A; Department of Pathology, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, University of Paris, UMR 1141 Inserm, 75010 Paris, France.
  • Némati F; Department of Genetics, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Roman-Roman S; Department of Genetics, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Bourdeaut F; Laboratory of Preclinical Investigation, Translational Research Department, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Adle-Biassette H; Department of Translational Research, Institut Curie, University of Paris Saclay, 75005 Paris, France.
  • Mammar H; Integrated Cancer Research Site, Institut Curie, 75005 Paris, France.
  • Froelich S; Department of Pathology, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, University of Paris, UMR 1141 Inserm, 75010 Paris, France.
  • Bièche I; Proton Therapy Center, Institut Curie, 91400 Orsay, France.
  • Decaudin D; Department of Neurosurgery, Lariboisière Hospital, Assistance Publique des Hôpitaux de Paris, University of Paris, 75010 Paris, France.
Cancers (Basel) ; 14(6)2022 Mar 14.
Article en En | MEDLINE | ID: mdl-35326637
ABSTRACT
Chordomas are rare neoplasms characterized by a high recurrence rate and a poor long-term prognosis. Considering their chemo-/radio-resistance, alternative treatment strategies are strongly required, but their development is limited by the paucity of relevant preclinical models. Mutations affecting genes of the SWI/SNF complexes are frequently found in chordomas, suggesting a potential therapeutic effect of epigenetic regulators in this pathology. Twelve PDX models were established and characterized on histological and biomolecular features. Patients whose tumors were able to grow into mice had a statistically significant lower progression-free survival than those whose tumors did not grow after in vivo transplantation (p = 0.007). All PDXs maintained the same histopathological features as patients' tumors. Homozygous deletions of CDKN2A/2B (58.3%) and PBRM1 (25%) variants were the most common genomic alterations found. In the tazemetostat treated PDX model harboring a PBRM1 variant, an overall survival of 100% was observed. Our panel of chordoma PDXs represents a useful preclinical tool for both pharmacologic and biological assessments. The first demonstration of a high antitumor activity of tazemetostat in a PDX model harboring a PBRM1 variant supports further evaluation for EZH2-inhibitors in this subgroup of chordomas.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2022 Tipo del documento: Article País de afiliación: Francia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2022 Tipo del documento: Article País de afiliación: Francia