In vivo evaluation of the EZH2 inhibitor (EPZ011989) alone or in combination with standard of care cytotoxic agents against pediatric malignant rhabdoid tumor preclinical models-A report from the Pediatric Preclinical Testing Consortium

Pediatr Blood Cancer. 2021 Feb;68(2):e28772. doi: 10.1002/pbc.28772. Epub 2020 Oct 22.

Abstract

The Pediatric Preclinical Testing Program (PPTP) previously reported the activity of the EZH2 inhibitor tazemetostat (EPZ6438) against xenograft models of rhabdoid tumors. Here, we determined whether an inhibitor of EZH2 enhanced the effect of standard of care chemotherapeutic agents: irinotecan, vincristine, and cyclophosphamide. EPZ011989 significantly prolonged time to event in all the six rhabdoid models studied but did not induce tumor regression. The addition of EPZ011989 to standard of care agents significantly improved time to event in at least one model for each of the agents studied, although this effect was observed in only a minority of the combination testing experiments.

Keywords: pediatric cancer; rhabdomyosarcoma; xenograft models.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Benzamides / pharmacology
  • Biphenyl Compounds / pharmacology
  • Cell Line, Tumor
  • Cyclophosphamide / pharmacology
  • Drug Synergism
  • Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors*
  • Female
  • Humans
  • Irinotecan / pharmacology
  • Mice
  • Mice, SCID
  • Morpholines / pharmacology
  • Pyridones / pharmacology
  • Rhabdomyosarcoma / drug therapy*
  • Rhabdomyosarcoma / pathology
  • Vincristine / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Benzamides
  • Biphenyl Compounds
  • Morpholines
  • Pyridones
  • Vincristine
  • Irinotecan
  • Cyclophosphamide
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse
  • tazemetostat